Molecule Information
General Information of the Molecule (ID: Mol00856)
Name |
Catalase-peroxidase (KATG)
,Mycobacterium tuberculosis
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Synonyms |
CP; Peroxidase/catalase; Rv1908c; MTCY180.10
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Molecule Type |
Protein
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Gene Name |
katG
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Gene ID | |||||
Sequence |
MPEQHPPITETTTGAASNGCPVVGHMKYPVEGGGNQDWWPNRLNLKVLHQNPAVADPMGA
AFDYAAEVATIDVDALTRDIEEVMTTSQPWWPADYGHYGPLFIRMAWHAAGTYRIHDGRG GAGGGMQRFAPLNSWPDNASLDKARRLLWPVKKKYGKKLSWADLIVFAGNCALESMGFKT FGFGFGRVDQWEPDEVYWGKEATWLGDERYSGKRDLENPLAAVQMGLIYVNPEGPNGNPD PMAAAVDIRETFRRMAMNDVETAALIVGGHTFGKTHGAGPADLVGPEPEAAPLEQMGLGW KSSYGTGTGKDAITSGIEVVWTNTPTKWDNSFLEILYGYEWELTKSPAGAWQYTAKDGAG AGTIPDPFGGPGRSPTMLATDLSLRVDPIYERITRRWLEHPEELADEFAKAWYKLIHRDM GPVARYLGPLVPKQTLLWQDPVPAVSHDLVGEAEIASLKSQIRASGLTVSQLVSTAWAAA SSFRGSDKRGGANGGRIRLQPQVGWEVNDPDGDLRKVIRTLEEIQESFNSAAPGNIKVSF ADLVVLGGCAAIEKAAKAAGHNITVPFTPGRTDASQEQTDVESFAVLEPKADGFRNYLGK GNPLPAEYMLLDKANLLTLSAPEMTVLVGGLRVLGANYKRLPLGVFTEASESLTNDFFVN LLDMGITWEPSPADDGTYQGKDGSGKVKWTGSRVDLVFGSNSELRALVEVYGADDAQPKF VQDFVAAWDKVMNLDRFDVR Click to Show/Hide
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Function |
Bifunctional enzyme with both catalase and broad-spectrum peroxidase activity, oxidizing various electron donors including NADP(H). Protects M.tuberculosis against toxic reactive oxygen species (ROS) including hydrogen peroxide as well as organic peroxides and thus contributes to its survival within host macrophages by countering the phagocyte oxidative burst. Also displays efficient peroxynitritase activity, which may help the bacterium to persist in macrophages.
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Uniprot ID | |||||
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Type(s) of Resistant Mechanism of This Molecule
DISM: Drug Inactivation by Structure Modification
UAPP: Unusual Activation of Pro-survival Pathway
Drug Resistance Data Categorized by Drug
Approved Drug(s)
2 drug(s) in total
Isoniazid
Drug Resistance Data Categorized by Their Corresponding Mechanisms | ||||
Drug Inactivation by Structure Modification (DISM) | ||||
Disease Class: HIV-infected patients with tuberculosis | [1] | |||
Resistant Disease | HIV-infected patients with tuberculosis [ICD-11: 1C60.0] | |||
Resistant Drug | Isoniazid | |||
Molecule Alteration | Expression | Down-regulation |
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Experimental Note | Discovered Using In-vivo Testing Model | |||
Cell Pathway Regulation | Cell growth | Inhibition | hsa05200 | |
In Vitro Model | Mycobacterium smegmatis mc2155 | 246196 | ||
Mycobacterium smegmatis mc2155-Cu | 246196 | |||
Experiment for Molecule Alteration |
qPCR | |||
Experiment for Drug Resistance |
MIC assay | |||
Mechanism Description | As a prodrug, INH needs to be activated by katG to execute its antibiotic function. katG is a bifunctional enzyme with both catalase and peroxidase activity and catalyzes the coupling of INH with NAD+ to form the isonicotinic acyl-NAD complex, which binds to the enoyl-acyl carrier protein reductase to inhibit the synthesis of mycolic acid required for the mycobacterial cell wall. In the present study, quantitative proteomic analysis showed that the expression level of katG was down-regulated in mc2155-Cu as compared to mc2155. Down-regulation of katG expression as well as a decrease in cellular NAD level results in the higher resistance to INH in mc2155-Cu. | |||
Disease Class: Pneumoconiosis complicated with tuberculosis | [2] | |||
Resistant Disease | Pneumoconiosis complicated with tuberculosis [ICD-11: CA60.Y] | |||
Resistant Drug | Isoniazid | |||
Molecule Alteration | Missense mutation | p.S315T |
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Experimental Note | Identified from the Human Clinical Data | |||
In Vitro Model | Mycobacterium tuberculosis isolates | 1773 | ||
Mycobacterium tuberculosis H37Rv1 | 1773 | |||
Experiment for Molecule Alteration |
qRT-PCR | |||
Mechanism Description | Isoniazid is a hydrazine chemical synthetic drug, which is able to be oxidized to isonicotinic acid by the catalase-peroxidase encoded by the katG gene that participates in the synthesis of coenzyme I (NAD) to inhibit the biosynthesis of mycolic acid of the cell wall in Mycobacterium tuberculosis, so as to damage the MDR-TB's barricade of resisting antioxygen and invasion. Due to deletion or mutation in the katG gene, resistance is able to be generated as the enzymatic activity is lost or degraded, thus, inhibiting the activation of Isoniazid. | |||
Disease Class: Pneumoconiosis complicated with tuberculosis | [2] | |||
Resistant Disease | Pneumoconiosis complicated with tuberculosis [ICD-11: CA60.Y] | |||
Resistant Drug | Isoniazid | |||
Molecule Alteration | Missense mutation | p.S315N |
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Experimental Note | Identified from the Human Clinical Data | |||
In Vitro Model | Mycobacterium tuberculosis isolates | 1773 | ||
Mycobacterium tuberculosis H37Rv1 | 1773 | |||
Experiment for Molecule Alteration |
qRT-PCR | |||
Mechanism Description | Isoniazid is a hydrazine chemical synthetic drug, which is able to be oxidized to isonicotinic acid by the catalase-peroxidase encoded by the katG gene that participates in the synthesis of coenzyme I (NAD) to inhibit the biosynthesis of mycolic acid of the cell wall in Mycobacterium tuberculosis, so as to damage the MDR-TB's barricade of resisting antioxygen and invasion. Due to deletion or mutation in the katG gene, resistance is able to be generated as the enzymatic activity is lost or degraded, thus, inhibiting the activation of Isoniazid. | |||
Disease Class: Pneumoconiosis complicated with tuberculosis | [2] | |||
Resistant Disease | Pneumoconiosis complicated with tuberculosis [ICD-11: CA60.Y] | |||
Resistant Drug | Isoniazid | |||
Molecule Alteration | Missense mutation | p.A431V |
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Experimental Note | Identified from the Human Clinical Data | |||
In Vitro Model | Mycobacterium tuberculosis isolates | 1773 | ||
Mycobacterium tuberculosis H37Rv1 | 1773 | |||
Experiment for Molecule Alteration |
qRT-PCR | |||
Mechanism Description | Isoniazid is a hydrazine chemical synthetic drug, which is able to be oxidized to isonicotinic acid by the catalase-peroxidase encoded by the katG gene that participates in the synthesis of coenzyme I (NAD) to inhibit the biosynthesis of mycolic acid of the cell wall in Mycobacterium tuberculosis, so as to damage the MDR-TB's barricade of resisting antioxygen and invasion. Due to deletion or mutation in the katG gene, resistance is able to be generated as the enzymatic activity is lost or degraded, thus, inhibiting the activation of Isoniazid. | |||
Disease Class: Mycolicibacterium smegmatis infection | [3] | |||
Resistant Disease | Mycolicibacterium smegmatis infection [ICD-11: 1B2Z.6] | |||
Resistant Drug | Isoniazid | |||
Molecule Alteration | Missense mutation | p.S315T |
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Experimental Note | Discovered Using In-vivo Testing Model | |||
In Vitro Model | Mycobacterium tuberculosis strain H37Rv ATCC27294 T | 83332 | ||
Experiment for Molecule Alteration |
Sequencing analysis | |||
Experiment for Drug Resistance |
In vitro drug susceptibility testing | |||
Mechanism Description | Notably, isoniazid is activated by the enzyme catalase-peroxidase, KatG, encoded by katG, whereas prothionamide is activated by the flavin monoxygenase, EthA, encoded by ethA. Mutations in katG and ethA are associated with individual isoniazid and prothionamide/ethionamide resistance, respectively. The ndh gene coding for NADH dehydrogenase, Ndh, was first identified as a new mechanism for INHR in Mycobacterium smegmatis. The mutations in ndh gene cause defects in the oxidation of NADH to NAD, which results in NADH accumulation and NAD depletion. The increased level of NADH inhibits the binding of isoniazid-NAD adduct to the active site of the InhA enzyme, which disturbs the regulation of enzyme activity and may cause co-resistance to isoniazid and prothionamide. EthR, a member of the TetR/CamR family, is a repressor of ethA. EthR regulates the transcription of ethA by coordinated octamerization on a 55-bp operator situated in the ethA-R intergenic region. Impeding EthR function leads to enhanced mycobacterial sensitivity to prothionamide, whereas mutations in ethR encoding a negative transcriptional regulator of the expression of EthA lead to prothionamide resistance. Finally, MshA, a member of the glycosyltransferase family, is a key enzyme involved in mycothiol biosynthesis in M. tuberculosis. Mutations in mshA coding MshA have been proposed to create a disturbance in prothionamide/ethionamide activation. | |||
Disease Class: Mycolicibacterium smegmatis infection | [3] | |||
Resistant Disease | Mycolicibacterium smegmatis infection [ICD-11: 1B2Z.6] | |||
Resistant Drug | Isoniazid | |||
Molecule Alteration | Missense mutation | p.S315N |
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Experimental Note | Discovered Using In-vivo Testing Model | |||
In Vitro Model | Mycobacterium tuberculosis strain H37Rv ATCC27294 T | 83332 | ||
Experiment for Molecule Alteration |
Sequencing analysis | |||
Experiment for Drug Resistance |
In vitro drug susceptibility testing | |||
Mechanism Description | Notably, isoniazid is activated by the enzyme catalase-peroxidase, KatG, encoded by katG, whereas prothionamide is activated by the flavin monoxygenase, EthA, encoded by ethA. Mutations in katG and ethA are associated with individual isoniazid and prothionamide/ethionamide resistance, respectively. The ndh gene coding for NADH dehydrogenase, Ndh, was first identified as a new mechanism for INHR in Mycobacterium smegmatis. The mutations in ndh gene cause defects in the oxidation of NADH to NAD, which results in NADH accumulation and NAD depletion. The increased level of NADH inhibits the binding of isoniazid-NAD adduct to the active site of the InhA enzyme, which disturbs the regulation of enzyme activity and may cause co-resistance to isoniazid and prothionamide. EthR, a member of the TetR/CamR family, is a repressor of ethA. EthR regulates the transcription of ethA by coordinated octamerization on a 55-bp operator situated in the ethA-R intergenic region. Impeding EthR function leads to enhanced mycobacterial sensitivity to prothionamide, whereas mutations in ethR encoding a negative transcriptional regulator of the expression of EthA lead to prothionamide resistance. Finally, MshA, a member of the glycosyltransferase family, is a key enzyme involved in mycothiol biosynthesis in M. tuberculosis. Mutations in mshA coding MshA have been proposed to create a disturbance in prothionamide/ethionamide activation. | |||
Disease Class: Mycolicibacterium smegmatis infection | [3] | |||
Resistant Disease | Mycolicibacterium smegmatis infection [ICD-11: 1B2Z.6] | |||
Resistant Drug | Isoniazid | |||
Molecule Alteration | Missense mutation | p.A312P |
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Experimental Note | Discovered Using In-vivo Testing Model | |||
In Vitro Model | Mycobacterium tuberculosis strain H37Rv ATCC27294 T | 83332 | ||
Experiment for Molecule Alteration |
Sequencing analysis | |||
Experiment for Drug Resistance |
In vitro drug susceptibility testing | |||
Mechanism Description | Notably, isoniazid is activated by the enzyme catalase-peroxidase, KatG, encoded by katG, whereas prothionamide is activated by the flavin monoxygenase, EthA, encoded by ethA. Mutations in katG and ethA are associated with individual isoniazid and prothionamide/ethionamide resistance, respectively. The ndh gene coding for NADH dehydrogenase, Ndh, was first identified as a new mechanism for INHR in Mycobacterium smegmatis. The mutations in ndh gene cause defects in the oxidation of NADH to NAD, which results in NADH accumulation and NAD depletion. The increased level of NADH inhibits the binding of isoniazid-NAD adduct to the active site of the InhA enzyme, which disturbs the regulation of enzyme activity and may cause co-resistance to isoniazid and prothionamide. EthR, a member of the TetR/CamR family, is a repressor of ethA. EthR regulates the transcription of ethA by coordinated octamerization on a 55-bp operator situated in the ethA-R intergenic region. Impeding EthR function leads to enhanced mycobacterial sensitivity to prothionamide, whereas mutations in ethR encoding a negative transcriptional regulator of the expression of EthA lead to prothionamide resistance. Finally, MshA, a member of the glycosyltransferase family, is a key enzyme involved in mycothiol biosynthesis in M. tuberculosis. Mutations in mshA coding MshA have been proposed to create a disturbance in prothionamide/ethionamide activation. | |||
Disease Class: Mycolicibacterium smegmatis infection | [3] | |||
Resistant Disease | Mycolicibacterium smegmatis infection [ICD-11: 1B2Z.6] | |||
Resistant Drug | Isoniazid | |||
Molecule Alteration | Missense mutation | p.A264V |
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Experimental Note | Discovered Using In-vivo Testing Model | |||
In Vitro Model | Mycobacterium tuberculosis strain H37Rv ATCC27294 T | 83332 | ||
Experiment for Molecule Alteration |
Sequencing analysis | |||
Experiment for Drug Resistance |
In vitro drug susceptibility testing | |||
Mechanism Description | Notably, isoniazid is activated by the enzyme catalase-peroxidase, KatG, encoded by katG, whereas prothionamide is activated by the flavin monoxygenase, EthA, encoded by ethA. Mutations in katG and ethA are associated with individual isoniazid and prothionamide/ethionamide resistance, respectively. The ndh gene coding for NADH dehydrogenase, Ndh, was first identified as a new mechanism for INHR in Mycobacterium smegmatis. The mutations in ndh gene cause defects in the oxidation of NADH to NAD, which results in NADH accumulation and NAD depletion. The increased level of NADH inhibits the binding of isoniazid-NAD adduct to the active site of the InhA enzyme, which disturbs the regulation of enzyme activity and may cause co-resistance to isoniazid and prothionamide. EthR, a member of the TetR/CamR family, is a repressor of ethA. EthR regulates the transcription of ethA by coordinated octamerization on a 55-bp operator situated in the ethA-R intergenic region. Impeding EthR function leads to enhanced mycobacterial sensitivity to prothionamide, whereas mutations in ethR encoding a negative transcriptional regulator of the expression of EthA lead to prothionamide resistance. Finally, MshA, a member of the glycosyltransferase family, is a key enzyme involved in mycothiol biosynthesis in M. tuberculosis. Mutations in mshA coding MshA have been proposed to create a disturbance in prothionamide/ethionamide activation. | |||
Disease Class: Mycolicibacterium smegmatis infection | [3] | |||
Resistant Disease | Mycolicibacterium smegmatis infection [ICD-11: 1B2Z.6] | |||
Resistant Drug | Isoniazid | |||
Molecule Alteration | Missense mutation | p.N660D |
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Experimental Note | Discovered Using In-vivo Testing Model | |||
In Vitro Model | Mycobacterium tuberculosis strain H37Rv ATCC27294 T | 83332 | ||
Experiment for Molecule Alteration |
Sequencing analysis | |||
Experiment for Drug Resistance |
In vitro drug susceptibility testing | |||
Mechanism Description | Notably, isoniazid is activated by the enzyme catalase-peroxidase, KatG, encoded by katG, whereas prothionamide is activated by the flavin monoxygenase, EthA, encoded by ethA. Mutations in katG and ethA are associated with individual isoniazid and prothionamide/ethionamide resistance, respectively. The ndh gene coding for NADH dehydrogenase, Ndh, was first identified as a new mechanism for INHR in Mycobacterium smegmatis. The mutations in ndh gene cause defects in the oxidation of NADH to NAD, which results in NADH accumulation and NAD depletion. The increased level of NADH inhibits the binding of isoniazid-NAD adduct to the active site of the InhA enzyme, which disturbs the regulation of enzyme activity and may cause co-resistance to isoniazid and prothionamide. EthR, a member of the TetR/CamR family, is a repressor of ethA. EthR regulates the transcription of ethA by coordinated octamerization on a 55-bp operator situated in the ethA-R intergenic region. Impeding EthR function leads to enhanced mycobacterial sensitivity to prothionamide, whereas mutations in ethR encoding a negative transcriptional regulator of the expression of EthA lead to prothionamide resistance. Finally, MshA, a member of the glycosyltransferase family, is a key enzyme involved in mycothiol biosynthesis in M. tuberculosis. Mutations in mshA coding MshA have been proposed to create a disturbance in prothionamide/ethionamide activation. | |||
Disease Class: Mycolicibacterium smegmatis infection | [3] | |||
Resistant Disease | Mycolicibacterium smegmatis infection [ICD-11: 1B2Z.6] | |||
Resistant Drug | Isoniazid | |||
Molecule Alteration | Missense mutation | p.L147P |
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Experimental Note | Discovered Using In-vivo Testing Model | |||
In Vitro Model | Mycobacterium tuberculosis strain H37Rv ATCC27294 T | 83332 | ||
Experiment for Molecule Alteration |
Sequencing analysis | |||
Experiment for Drug Resistance |
In vitro drug susceptibility testing | |||
Mechanism Description | Notably, isoniazid is activated by the enzyme catalase-peroxidase, KatG, encoded by katG, whereas prothionamide is activated by the flavin monoxygenase, EthA, encoded by ethA. Mutations in katG and ethA are associated with individual isoniazid and prothionamide/ethionamide resistance, respectively. The ndh gene coding for NADH dehydrogenase, Ndh, was first identified as a new mechanism for INHR in Mycobacterium smegmatis. The mutations in ndh gene cause defects in the oxidation of NADH to NAD, which results in NADH accumulation and NAD depletion. The increased level of NADH inhibits the binding of isoniazid-NAD adduct to the active site of the InhA enzyme, which disturbs the regulation of enzyme activity and may cause co-resistance to isoniazid and prothionamide. EthR, a member of the TetR/CamR family, is a repressor of ethA. EthR regulates the transcription of ethA by coordinated octamerization on a 55-bp operator situated in the ethA-R intergenic region. Impeding EthR function leads to enhanced mycobacterial sensitivity to prothionamide, whereas mutations in ethR encoding a negative transcriptional regulator of the expression of EthA lead to prothionamide resistance. Finally, MshA, a member of the glycosyltransferase family, is a key enzyme involved in mycothiol biosynthesis in M. tuberculosis. Mutations in mshA coding MshA have been proposed to create a disturbance in prothionamide/ethionamide activation. | |||
Disease Class: Mycolicibacterium smegmatis infection | [3] | |||
Resistant Disease | Mycolicibacterium smegmatis infection [ICD-11: 1B2Z.6] | |||
Resistant Drug | Isoniazid | |||
Molecule Alteration | Missense mutation | p.C20R |
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Experimental Note | Discovered Using In-vivo Testing Model | |||
In Vitro Model | Mycobacterium tuberculosis strain H37Rv ATCC27294 T | 83332 | ||
Experiment for Molecule Alteration |
Sequencing analysis | |||
Experiment for Drug Resistance |
In vitro drug susceptibility testing | |||
Mechanism Description | Notably, isoniazid is activated by the enzyme catalase-peroxidase, KatG, encoded by katG, whereas prothionamide is activated by the flavin monoxygenase, EthA, encoded by ethA. Mutations in katG and ethA are associated with individual isoniazid and prothionamide/ethionamide resistance, respectively. The ndh gene coding for NADH dehydrogenase, Ndh, was first identified as a new mechanism for INHR in Mycobacterium smegmatis. The mutations in ndh gene cause defects in the oxidation of NADH to NAD, which results in NADH accumulation and NAD depletion. The increased level of NADH inhibits the binding of isoniazid-NAD adduct to the active site of the InhA enzyme, which disturbs the regulation of enzyme activity and may cause co-resistance to isoniazid and prothionamide. EthR, a member of the TetR/CamR family, is a repressor of ethA. EthR regulates the transcription of ethA by coordinated octamerization on a 55-bp operator situated in the ethA-R intergenic region. Impeding EthR function leads to enhanced mycobacterial sensitivity to prothionamide, whereas mutations in ethR encoding a negative transcriptional regulator of the expression of EthA lead to prothionamide resistance. Finally, MshA, a member of the glycosyltransferase family, is a key enzyme involved in mycothiol biosynthesis in M. tuberculosis. Mutations in mshA coding MshA have been proposed to create a disturbance in prothionamide/ethionamide activation. | |||
Disease Class: Mycolicibacterium smegmatis infection | [3] | |||
Resistant Disease | Mycolicibacterium smegmatis infection [ICD-11: 1B2Z.6] | |||
Resistant Drug | Isoniazid | |||
Molecule Alteration | Missense mutation | p.S315T |
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Experimental Note | Discovered Using In-vivo Testing Model | |||
In Vitro Model | Mycobacterium tuberculosis strain H37Rv ATCC27294 T | 83332 | ||
Experiment for Molecule Alteration |
Sequencing analysis | |||
Experiment for Drug Resistance |
In vitro drug susceptibility testing | |||
Mechanism Description | Notably, isoniazid is activated by the enzyme catalase-peroxidase, KatG, encoded by katG, whereas prothionamide is activated by the flavin monoxygenase, EthA, encoded by ethA. Mutations in katG and ethA are associated with individual isoniazid and prothionamide/ethionamide resistance, respectively. The ndh gene coding for NADH dehydrogenase, Ndh, was first identified as a new mechanism for INHR in Mycobacterium smegmatis. The mutations in ndh gene cause defects in the oxidation of NADH to NAD, which results in NADH accumulation and NAD depletion. The increased level of NADH inhibits the binding of isoniazid-NAD adduct to the active site of the InhA enzyme, which disturbs the regulation of enzyme activity and may cause co-resistance to isoniazid and prothionamide. EthR, a member of the TetR/CamR family, is a repressor of ethA. EthR regulates the transcription of ethA by coordinated octamerization on a 55-bp operator situated in the ethA-R intergenic region. Impeding EthR function leads to enhanced mycobacterial sensitivity to prothionamide, whereas mutations in ethR encoding a negative transcriptional regulator of the expression of EthA lead to prothionamide resistance. Finally, MshA, a member of the glycosyltransferase family, is a key enzyme involved in mycothiol biosynthesis in M. tuberculosis. Mutations in mshA coding MshA have been proposed to create a disturbance in prothionamide/ethionamide activation. | |||
Disease Class: Mycolicibacterium smegmatis infection | [3] | |||
Resistant Disease | Mycolicibacterium smegmatis infection [ICD-11: 1B2Z.6] | |||
Resistant Drug | Isoniazid | |||
Molecule Alteration | Missense mutation | p.T308P |
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Experimental Note | Discovered Using In-vivo Testing Model | |||
In Vitro Model | Mycobacterium tuberculosis strain H37Rv ATCC27294 T | 83332 | ||
Experiment for Molecule Alteration |
Sequencing analysis | |||
Experiment for Drug Resistance |
In vitro drug susceptibility testing | |||
Mechanism Description | Notably, isoniazid is activated by the enzyme catalase-peroxidase, KatG, encoded by katG, whereas prothionamide is activated by the flavin monoxygenase, EthA, encoded by ethA. Mutations in katG and ethA are associated with individual isoniazid and prothionamide/ethionamide resistance, respectively. The ndh gene coding for NADH dehydrogenase, Ndh, was first identified as a new mechanism for INHR in Mycobacterium smegmatis. The mutations in ndh gene cause defects in the oxidation of NADH to NAD, which results in NADH accumulation and NAD depletion. The increased level of NADH inhibits the binding of isoniazid-NAD adduct to the active site of the InhA enzyme, which disturbs the regulation of enzyme activity and may cause co-resistance to isoniazid and prothionamide. EthR, a member of the TetR/CamR family, is a repressor of ethA. EthR regulates the transcription of ethA by coordinated octamerization on a 55-bp operator situated in the ethA-R intergenic region. Impeding EthR function leads to enhanced mycobacterial sensitivity to prothionamide, whereas mutations in ethR encoding a negative transcriptional regulator of the expression of EthA lead to prothionamide resistance. Finally, MshA, a member of the glycosyltransferase family, is a key enzyme involved in mycothiol biosynthesis in M. tuberculosis. Mutations in mshA coding MshA have been proposed to create a disturbance in prothionamide/ethionamide activation. | |||
Disease Class: Mycolicibacterium smegmatis infection | [3] | |||
Resistant Disease | Mycolicibacterium smegmatis infection [ICD-11: 1B2Z.6] | |||
Resistant Drug | Isoniazid | |||
Molecule Alteration | Missense mutation | p.T275A |
||
Experimental Note | Discovered Using In-vivo Testing Model | |||
In Vitro Model | Mycobacterium tuberculosis strain H37Rv ATCC27294 T | 83332 | ||
Experiment for Molecule Alteration |
Sequencing analysis | |||
Experiment for Drug Resistance |
In vitro drug susceptibility testing | |||
Mechanism Description | Notably, isoniazid is activated by the enzyme catalase-peroxidase, KatG, encoded by katG, whereas prothionamide is activated by the flavin monoxygenase, EthA, encoded by ethA. Mutations in katG and ethA are associated with individual isoniazid and prothionamide/ethionamide resistance, respectively. The ndh gene coding for NADH dehydrogenase, Ndh, was first identified as a new mechanism for INHR in Mycobacterium smegmatis. The mutations in ndh gene cause defects in the oxidation of NADH to NAD, which results in NADH accumulation and NAD depletion. The increased level of NADH inhibits the binding of isoniazid-NAD adduct to the active site of the InhA enzyme, which disturbs the regulation of enzyme activity and may cause co-resistance to isoniazid and prothionamide. EthR, a member of the TetR/CamR family, is a repressor of ethA. EthR regulates the transcription of ethA by coordinated octamerization on a 55-bp operator situated in the ethA-R intergenic region. Impeding EthR function leads to enhanced mycobacterial sensitivity to prothionamide, whereas mutations in ethR encoding a negative transcriptional regulator of the expression of EthA lead to prothionamide resistance. Finally, MshA, a member of the glycosyltransferase family, is a key enzyme involved in mycothiol biosynthesis in M. tuberculosis. Mutations in mshA coding MshA have been proposed to create a disturbance in prothionamide/ethionamide activation. | |||
Disease Class: Mycolicibacterium smegmatis infection | [3] | |||
Resistant Disease | Mycolicibacterium smegmatis infection [ICD-11: 1B2Z.6] | |||
Resistant Drug | Isoniazid | |||
Molecule Alteration | Missense mutation | p.S315T |
||
Experimental Note | Discovered Using In-vivo Testing Model | |||
In Vitro Model | Mycobacterium tuberculosis strain H37Rv ATCC27294 T | 83332 | ||
Experiment for Molecule Alteration |
Sequencing analysis | |||
Experiment for Drug Resistance |
In vitro drug susceptibility testing | |||
Mechanism Description | Notably, isoniazid is activated by the enzyme catalase-peroxidase, KatG, encoded by katG, whereas prothionamide is activated by the flavin monoxygenase, EthA, encoded by ethA. Mutations in katG and ethA are associated with individual isoniazid and prothionamide/ethionamide resistance, respectively. The ndh gene coding for NADH dehydrogenase, Ndh, was first identified as a new mechanism for INHR in Mycobacterium smegmatis. The mutations in ndh gene cause defects in the oxidation of NADH to NAD, which results in NADH accumulation and NAD depletion. The increased level of NADH inhibits the binding of isoniazid-NAD adduct to the active site of the InhA enzyme, which disturbs the regulation of enzyme activity and may cause co-resistance to isoniazid and prothionamide. EthR, a member of the TetR/CamR family, is a repressor of ethA. EthR regulates the transcription of ethA by coordinated octamerization on a 55-bp operator situated in the ethA-R intergenic region. Impeding EthR function leads to enhanced mycobacterial sensitivity to prothionamide, whereas mutations in ethR encoding a negative transcriptional regulator of the expression of EthA lead to prothionamide resistance. Finally, MshA, a member of the glycosyltransferase family, is a key enzyme involved in mycothiol biosynthesis in M. tuberculosis. Mutations in mshA coding MshA have been proposed to create a disturbance in prothionamide/ethionamide activation. | |||
Disease Class: Mycolicibacterium smegmatis infection | [3] | |||
Resistant Disease | Mycolicibacterium smegmatis infection [ICD-11: 1B2Z.6] | |||
Resistant Drug | Isoniazid | |||
Molecule Alteration | Missense mutation | p.D142G |
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Experimental Note | Discovered Using In-vivo Testing Model | |||
In Vitro Model | Mycobacterium tuberculosis strain H37Rv ATCC27294 T | 83332 | ||
Experiment for Molecule Alteration |
Sequencing analysis | |||
Experiment for Drug Resistance |
In vitro drug susceptibility testing | |||
Mechanism Description | Notably, isoniazid is activated by the enzyme catalase-peroxidase, KatG, encoded by katG, whereas prothionamide is activated by the flavin monoxygenase, EthA, encoded by ethA. Mutations in katG and ethA are associated with individual isoniazid and prothionamide/ethionamide resistance, respectively. The ndh gene coding for NADH dehydrogenase, Ndh, was first identified as a new mechanism for INHR in Mycobacterium smegmatis. The mutations in ndh gene cause defects in the oxidation of NADH to NAD, which results in NADH accumulation and NAD depletion. The increased level of NADH inhibits the binding of isoniazid-NAD adduct to the active site of the InhA enzyme, which disturbs the regulation of enzyme activity and may cause co-resistance to isoniazid and prothionamide. EthR, a member of the TetR/CamR family, is a repressor of ethA. EthR regulates the transcription of ethA by coordinated octamerization on a 55-bp operator situated in the ethA-R intergenic region. Impeding EthR function leads to enhanced mycobacterial sensitivity to prothionamide, whereas mutations in ethR encoding a negative transcriptional regulator of the expression of EthA lead to prothionamide resistance. Finally, MshA, a member of the glycosyltransferase family, is a key enzyme involved in mycothiol biosynthesis in M. tuberculosis. Mutations in mshA coding MshA have been proposed to create a disturbance in prothionamide/ethionamide activation. | |||
Disease Class: Mycolicibacterium smegmatis infection | [3] | |||
Resistant Disease | Mycolicibacterium smegmatis infection [ICD-11: 1B2Z.6] | |||
Resistant Drug | Isoniazid | |||
Molecule Alteration | Missense mutation | p.S211G |
||
Experimental Note | Discovered Using In-vivo Testing Model | |||
In Vitro Model | Mycobacterium tuberculosis strain H37Rv ATCC27294 T | 83332 | ||
Experiment for Molecule Alteration |
Sequencing analysis | |||
Experiment for Drug Resistance |
In vitro drug susceptibility testing | |||
Mechanism Description | Notably, isoniazid is activated by the enzyme catalase-peroxidase, KatG, encoded by katG, whereas prothionamide is activated by the flavin monoxygenase, EthA, encoded by ethA. Mutations in katG and ethA are associated with individual isoniazid and prothionamide/ethionamide resistance, respectively. The ndh gene coding for NADH dehydrogenase, Ndh, was first identified as a new mechanism for INHR in Mycobacterium smegmatis. The mutations in ndh gene cause defects in the oxidation of NADH to NAD, which results in NADH accumulation and NAD depletion. The increased level of NADH inhibits the binding of isoniazid-NAD adduct to the active site of the InhA enzyme, which disturbs the regulation of enzyme activity and may cause co-resistance to isoniazid and prothionamide. EthR, a member of the TetR/CamR family, is a repressor of ethA. EthR regulates the transcription of ethA by coordinated octamerization on a 55-bp operator situated in the ethA-R intergenic region. Impeding EthR function leads to enhanced mycobacterial sensitivity to prothionamide, whereas mutations in ethR encoding a negative transcriptional regulator of the expression of EthA lead to prothionamide resistance. Finally, MshA, a member of the glycosyltransferase family, is a key enzyme involved in mycothiol biosynthesis in M. tuberculosis. Mutations in mshA coding MshA have been proposed to create a disturbance in prothionamide/ethionamide activation. | |||
Disease Class: Mycolicibacterium smegmatis infection | [3] | |||
Resistant Disease | Mycolicibacterium smegmatis infection [ICD-11: 1B2Z.6] | |||
Resistant Drug | Isoniazid | |||
Molecule Alteration | Missense mutation | p.S315T |
||
Experimental Note | Discovered Using In-vivo Testing Model | |||
In Vitro Model | Mycobacterium tuberculosis strain H37Rv ATCC27294 T | 83332 | ||
Experiment for Molecule Alteration |
Sequencing analysis | |||
Experiment for Drug Resistance |
In vitro drug susceptibility testing | |||
Mechanism Description | Notably, isoniazid is activated by the enzyme catalase-peroxidase, KatG, encoded by katG, whereas prothionamide is activated by the flavin monoxygenase, EthA, encoded by ethA. Mutations in katG and ethA are associated with individual isoniazid and prothionamide/ethionamide resistance, respectively. The ndh gene coding for NADH dehydrogenase, Ndh, was first identified as a new mechanism for INHR in Mycobacterium smegmatis. The mutations in ndh gene cause defects in the oxidation of NADH to NAD, which results in NADH accumulation and NAD depletion. The increased level of NADH inhibits the binding of isoniazid-NAD adduct to the active site of the InhA enzyme, which disturbs the regulation of enzyme activity and may cause co-resistance to isoniazid and prothionamide. EthR, a member of the TetR/CamR family, is a repressor of ethA. EthR regulates the transcription of ethA by coordinated octamerization on a 55-bp operator situated in the ethA-R intergenic region. Impeding EthR function leads to enhanced mycobacterial sensitivity to prothionamide, whereas mutations in ethR encoding a negative transcriptional regulator of the expression of EthA lead to prothionamide resistance. Finally, MshA, a member of the glycosyltransferase family, is a key enzyme involved in mycothiol biosynthesis in M. tuberculosis. Mutations in mshA coding MshA have been proposed to create a disturbance in prothionamide/ethionamide activation. | |||
Disease Class: Mycolicibacterium smegmatis infection | [3] | |||
Resistant Disease | Mycolicibacterium smegmatis infection [ICD-11: 1B2Z.6] | |||
Resistant Drug | Isoniazid | |||
Molecule Alteration | Missense mutation | p.M126I |
||
Experimental Note | Discovered Using In-vivo Testing Model | |||
In Vitro Model | Mycobacterium tuberculosis strain H37Rv ATCC27294 T | 83332 | ||
Experiment for Molecule Alteration |
Sequencing analysis | |||
Experiment for Drug Resistance |
In vitro drug susceptibility testing | |||
Mechanism Description | Notably, isoniazid is activated by the enzyme catalase-peroxidase, KatG, encoded by katG, whereas prothionamide is activated by the flavin monoxygenase, EthA, encoded by ethA. Mutations in katG and ethA are associated with individual isoniazid and prothionamide/ethionamide resistance, respectively. The ndh gene coding for NADH dehydrogenase, Ndh, was first identified as a new mechanism for INHR in Mycobacterium smegmatis. The mutations in ndh gene cause defects in the oxidation of NADH to NAD, which results in NADH accumulation and NAD depletion. The increased level of NADH inhibits the binding of isoniazid-NAD adduct to the active site of the InhA enzyme, which disturbs the regulation of enzyme activity and may cause co-resistance to isoniazid and prothionamide. EthR, a member of the TetR/CamR family, is a repressor of ethA. EthR regulates the transcription of ethA by coordinated octamerization on a 55-bp operator situated in the ethA-R intergenic region. Impeding EthR function leads to enhanced mycobacterial sensitivity to prothionamide, whereas mutations in ethR encoding a negative transcriptional regulator of the expression of EthA lead to prothionamide resistance. Finally, MshA, a member of the glycosyltransferase family, is a key enzyme involved in mycothiol biosynthesis in M. tuberculosis. Mutations in mshA coding MshA have been proposed to create a disturbance in prothionamide/ethionamide activation. | |||
Disease Class: Mycolicibacterium smegmatis infection | [3] | |||
Resistant Disease | Mycolicibacterium smegmatis infection [ICD-11: 1B2Z.6] | |||
Resistant Drug | Isoniazid | |||
Molecule Alteration | Missense mutation | p.W91R |
||
Experimental Note | Discovered Using In-vivo Testing Model | |||
In Vitro Model | Mycobacterium tuberculosis strain H37Rv ATCC27294 T | 83332 | ||
Experiment for Molecule Alteration |
Sequencing analysis | |||
Experiment for Drug Resistance |
In vitro drug susceptibility testing | |||
Mechanism Description | Notably, isoniazid is activated by the enzyme catalase-peroxidase, KatG, encoded by katG, whereas prothionamide is activated by the flavin monoxygenase, EthA, encoded by ethA. Mutations in katG and ethA are associated with individual isoniazid and prothionamide/ethionamide resistance, respectively. The ndh gene coding for NADH dehydrogenase, Ndh, was first identified as a new mechanism for INHR in Mycobacterium smegmatis. The mutations in ndh gene cause defects in the oxidation of NADH to NAD, which results in NADH accumulation and NAD depletion. The increased level of NADH inhibits the binding of isoniazid-NAD adduct to the active site of the InhA enzyme, which disturbs the regulation of enzyme activity and may cause co-resistance to isoniazid and prothionamide. EthR, a member of the TetR/CamR family, is a repressor of ethA. EthR regulates the transcription of ethA by coordinated octamerization on a 55-bp operator situated in the ethA-R intergenic region. Impeding EthR function leads to enhanced mycobacterial sensitivity to prothionamide, whereas mutations in ethR encoding a negative transcriptional regulator of the expression of EthA lead to prothionamide resistance. Finally, MshA, a member of the glycosyltransferase family, is a key enzyme involved in mycothiol biosynthesis in M. tuberculosis. Mutations in mshA coding MshA have been proposed to create a disturbance in prothionamide/ethionamide activation. | |||
Disease Class: Mycolicibacterium smegmatis infection | [3] | |||
Resistant Disease | Mycolicibacterium smegmatis infection [ICD-11: 1B2Z.6] | |||
Resistant Drug | Isoniazid | |||
Molecule Alteration | Missense mutation | p.S315G |
||
Experimental Note | Discovered Using In-vivo Testing Model | |||
In Vitro Model | Mycobacterium tuberculosis strain H37Rv ATCC27294 T | 83332 | ||
Experiment for Molecule Alteration |
Sequencing analysis | |||
Experiment for Drug Resistance |
In vitro drug susceptibility testing | |||
Mechanism Description | Notably, isoniazid is activated by the enzyme catalase-peroxidase, KatG, encoded by katG, whereas prothionamide is activated by the flavin monoxygenase, EthA, encoded by ethA. Mutations in katG and ethA are associated with individual isoniazid and prothionamide/ethionamide resistance, respectively. The ndh gene coding for NADH dehydrogenase, Ndh, was first identified as a new mechanism for INHR in Mycobacterium smegmatis. The mutations in ndh gene cause defects in the oxidation of NADH to NAD, which results in NADH accumulation and NAD depletion. The increased level of NADH inhibits the binding of isoniazid-NAD adduct to the active site of the InhA enzyme, which disturbs the regulation of enzyme activity and may cause co-resistance to isoniazid and prothionamide. EthR, a member of the TetR/CamR family, is a repressor of ethA. EthR regulates the transcription of ethA by coordinated octamerization on a 55-bp operator situated in the ethA-R intergenic region. Impeding EthR function leads to enhanced mycobacterial sensitivity to prothionamide, whereas mutations in ethR encoding a negative transcriptional regulator of the expression of EthA lead to prothionamide resistance. Finally, MshA, a member of the glycosyltransferase family, is a key enzyme involved in mycothiol biosynthesis in M. tuberculosis. Mutations in mshA coding MshA have been proposed to create a disturbance in prothionamide/ethionamide activation. | |||
Disease Class: Mycolicibacterium smegmatis infection | [3] | |||
Resistant Disease | Mycolicibacterium smegmatis infection [ICD-11: 1B2Z.6] | |||
Resistant Drug | Isoniazid | |||
Molecule Alteration | Missense mutation | p.G490S |
||
Experimental Note | Discovered Using In-vivo Testing Model | |||
In Vitro Model | Mycobacterium tuberculosis strain H37Rv ATCC27294 T | 83332 | ||
Experiment for Molecule Alteration |
Sequencing analysis | |||
Experiment for Drug Resistance |
In vitro drug susceptibility testing | |||
Mechanism Description | Notably, isoniazid is activated by the enzyme catalase-peroxidase, KatG, encoded by katG, whereas prothionamide is activated by the flavin monoxygenase, EthA, encoded by ethA. Mutations in katG and ethA are associated with individual isoniazid and prothionamide/ethionamide resistance, respectively. The ndh gene coding for NADH dehydrogenase, Ndh, was first identified as a new mechanism for INHR in Mycobacterium smegmatis. The mutations in ndh gene cause defects in the oxidation of NADH to NAD, which results in NADH accumulation and NAD depletion. The increased level of NADH inhibits the binding of isoniazid-NAD adduct to the active site of the InhA enzyme, which disturbs the regulation of enzyme activity and may cause co-resistance to isoniazid and prothionamide. EthR, a member of the TetR/CamR family, is a repressor of ethA. EthR regulates the transcription of ethA by coordinated octamerization on a 55-bp operator situated in the ethA-R intergenic region. Impeding EthR function leads to enhanced mycobacterial sensitivity to prothionamide, whereas mutations in ethR encoding a negative transcriptional regulator of the expression of EthA lead to prothionamide resistance. Finally, MshA, a member of the glycosyltransferase family, is a key enzyme involved in mycothiol biosynthesis in M. tuberculosis. Mutations in mshA coding MshA have been proposed to create a disturbance in prothionamide/ethionamide activation. | |||
Disease Class: Mycolicibacterium smegmatis infection | [3] | |||
Resistant Disease | Mycolicibacterium smegmatis infection [ICD-11: 1B2Z.6] | |||
Resistant Drug | Isoniazid | |||
Molecule Alteration | Missense mutation | p.S315T |
||
Experimental Note | Discovered Using In-vivo Testing Model | |||
In Vitro Model | Mycobacterium tuberculosis strain H37Rv ATCC27294 T | 83332 | ||
Experiment for Molecule Alteration |
Sequencing analysis | |||
Experiment for Drug Resistance |
In vitro drug susceptibility testing | |||
Mechanism Description | Notably, isoniazid is activated by the enzyme catalase-peroxidase, KatG, encoded by katG, whereas prothionamide is activated by the flavin monoxygenase, EthA, encoded by ethA. Mutations in katG and ethA are associated with individual isoniazid and prothionamide/ethionamide resistance, respectively. The ndh gene coding for NADH dehydrogenase, Ndh, was first identified as a new mechanism for INHR in Mycobacterium smegmatis. The mutations in ndh gene cause defects in the oxidation of NADH to NAD, which results in NADH accumulation and NAD depletion. The increased level of NADH inhibits the binding of isoniazid-NAD adduct to the active site of the InhA enzyme, which disturbs the regulation of enzyme activity and may cause co-resistance to isoniazid and prothionamide. EthR, a member of the TetR/CamR family, is a repressor of ethA. EthR regulates the transcription of ethA by coordinated octamerization on a 55-bp operator situated in the ethA-R intergenic region. Impeding EthR function leads to enhanced mycobacterial sensitivity to prothionamide, whereas mutations in ethR encoding a negative transcriptional regulator of the expression of EthA lead to prothionamide resistance. Finally, MshA, a member of the glycosyltransferase family, is a key enzyme involved in mycothiol biosynthesis in M. tuberculosis. Mutations in mshA coding MshA have been proposed to create a disturbance in prothionamide/ethionamide activation. | |||
Disease Class: Mycolicibacterium smegmatis infection | [3] | |||
Resistant Disease | Mycolicibacterium smegmatis infection [ICD-11: 1B2Z.6] | |||
Resistant Drug | Isoniazid | |||
Molecule Alteration | Missense mutation | p.V581G |
||
Experimental Note | Discovered Using In-vivo Testing Model | |||
In Vitro Model | Mycobacterium tuberculosis strain H37Rv ATCC27294 T | 83332 | ||
Experiment for Molecule Alteration |
Sequencing analysis | |||
Experiment for Drug Resistance |
In vitro drug susceptibility testing | |||
Mechanism Description | Notably, isoniazid is activated by the enzyme catalase-peroxidase, KatG, encoded by katG, whereas prothionamide is activated by the flavin monoxygenase, EthA, encoded by ethA. Mutations in katG and ethA are associated with individual isoniazid and prothionamide/ethionamide resistance, respectively. The ndh gene coding for NADH dehydrogenase, Ndh, was first identified as a new mechanism for INHR in Mycobacterium smegmatis. The mutations in ndh gene cause defects in the oxidation of NADH to NAD, which results in NADH accumulation and NAD depletion. The increased level of NADH inhibits the binding of isoniazid-NAD adduct to the active site of the InhA enzyme, which disturbs the regulation of enzyme activity and may cause co-resistance to isoniazid and prothionamide. EthR, a member of the TetR/CamR family, is a repressor of ethA. EthR regulates the transcription of ethA by coordinated octamerization on a 55-bp operator situated in the ethA-R intergenic region. Impeding EthR function leads to enhanced mycobacterial sensitivity to prothionamide, whereas mutations in ethR encoding a negative transcriptional regulator of the expression of EthA lead to prothionamide resistance. Finally, MshA, a member of the glycosyltransferase family, is a key enzyme involved in mycothiol biosynthesis in M. tuberculosis. Mutations in mshA coding MshA have been proposed to create a disturbance in prothionamide/ethionamide activation. | |||
Disease Class: Mycolicibacterium smegmatis infection | [3] | |||
Resistant Disease | Mycolicibacterium smegmatis infection [ICD-11: 1B2Z.6] | |||
Resistant Drug | Isoniazid | |||
Molecule Alteration | Missense mutation | p.A110V |
||
Experimental Note | Discovered Using In-vivo Testing Model | |||
In Vitro Model | Mycobacterium tuberculosis strain H37Rv ATCC27294 T | 83332 | ||
Experiment for Molecule Alteration |
Sequencing analysis | |||
Experiment for Drug Resistance |
In vitro drug susceptibility testing | |||
Mechanism Description | Notably, isoniazid is activated by the enzyme catalase-peroxidase, KatG, encoded by katG, whereas prothionamide is activated by the flavin monoxygenase, EthA, encoded by ethA. Mutations in katG and ethA are associated with individual isoniazid and prothionamide/ethionamide resistance, respectively. The ndh gene coding for NADH dehydrogenase, Ndh, was first identified as a new mechanism for INHR in Mycobacterium smegmatis. The mutations in ndh gene cause defects in the oxidation of NADH to NAD, which results in NADH accumulation and NAD depletion. The increased level of NADH inhibits the binding of isoniazid-NAD adduct to the active site of the InhA enzyme, which disturbs the regulation of enzyme activity and may cause co-resistance to isoniazid and prothionamide. EthR, a member of the TetR/CamR family, is a repressor of ethA. EthR regulates the transcription of ethA by coordinated octamerization on a 55-bp operator situated in the ethA-R intergenic region. Impeding EthR function leads to enhanced mycobacterial sensitivity to prothionamide, whereas mutations in ethR encoding a negative transcriptional regulator of the expression of EthA lead to prothionamide resistance. Finally, MshA, a member of the glycosyltransferase family, is a key enzyme involved in mycothiol biosynthesis in M. tuberculosis. Mutations in mshA coding MshA have been proposed to create a disturbance in prothionamide/ethionamide activation. | |||
Disease Class: Mycolicibacterium smegmatis infection | [3] | |||
Resistant Disease | Mycolicibacterium smegmatis infection [ICD-11: 1B2Z.6] | |||
Resistant Drug | Isoniazid | |||
Molecule Alteration | Missense mutation | p.S315T |
||
Experimental Note | Discovered Using In-vivo Testing Model | |||
In Vitro Model | Mycobacterium tuberculosis strain H37Rv ATCC27294 T | 83332 | ||
Experiment for Molecule Alteration |
Sequencing analysis | |||
Experiment for Drug Resistance |
In vitro drug susceptibility testing | |||
Mechanism Description | Notably, isoniazid is activated by the enzyme catalase-peroxidase, KatG, encoded by katG, whereas prothionamide is activated by the flavin monoxygenase, EthA, encoded by ethA. Mutations in katG and ethA are associated with individual isoniazid and prothionamide/ethionamide resistance, respectively. The ndh gene coding for NADH dehydrogenase, Ndh, was first identified as a new mechanism for INHR in Mycobacterium smegmatis. The mutations in ndh gene cause defects in the oxidation of NADH to NAD, which results in NADH accumulation and NAD depletion. The increased level of NADH inhibits the binding of isoniazid-NAD adduct to the active site of the InhA enzyme, which disturbs the regulation of enzyme activity and may cause co-resistance to isoniazid and prothionamide. EthR, a member of the TetR/CamR family, is a repressor of ethA. EthR regulates the transcription of ethA by coordinated octamerization on a 55-bp operator situated in the ethA-R intergenic region. Impeding EthR function leads to enhanced mycobacterial sensitivity to prothionamide, whereas mutations in ethR encoding a negative transcriptional regulator of the expression of EthA lead to prothionamide resistance. Finally, MshA, a member of the glycosyltransferase family, is a key enzyme involved in mycothiol biosynthesis in M. tuberculosis. Mutations in mshA coding MshA have been proposed to create a disturbance in prothionamide/ethionamide activation. | |||
Disease Class: Mycolicibacterium smegmatis infection | [3] | |||
Resistant Disease | Mycolicibacterium smegmatis infection [ICD-11: 1B2Z.6] | |||
Resistant Drug | Isoniazid | |||
Molecule Alteration | Missense mutation | p.G466R |
||
Experimental Note | Discovered Using In-vivo Testing Model | |||
In Vitro Model | Mycobacterium tuberculosis strain H37Rv ATCC27294 T | 83332 | ||
Experiment for Molecule Alteration |
Sequencing analysis | |||
Experiment for Drug Resistance |
In vitro drug susceptibility testing | |||
Mechanism Description | Notably, isoniazid is activated by the enzyme catalase-peroxidase, KatG, encoded by katG, whereas prothionamide is activated by the flavin monoxygenase, EthA, encoded by ethA. Mutations in katG and ethA are associated with individual isoniazid and prothionamide/ethionamide resistance, respectively. The ndh gene coding for NADH dehydrogenase, Ndh, was first identified as a new mechanism for INHR in Mycobacterium smegmatis. The mutations in ndh gene cause defects in the oxidation of NADH to NAD, which results in NADH accumulation and NAD depletion. The increased level of NADH inhibits the binding of isoniazid-NAD adduct to the active site of the InhA enzyme, which disturbs the regulation of enzyme activity and may cause co-resistance to isoniazid and prothionamide. EthR, a member of the TetR/CamR family, is a repressor of ethA. EthR regulates the transcription of ethA by coordinated octamerization on a 55-bp operator situated in the ethA-R intergenic region. Impeding EthR function leads to enhanced mycobacterial sensitivity to prothionamide, whereas mutations in ethR encoding a negative transcriptional regulator of the expression of EthA lead to prothionamide resistance. Finally, MshA, a member of the glycosyltransferase family, is a key enzyme involved in mycothiol biosynthesis in M. tuberculosis. Mutations in mshA coding MshA have been proposed to create a disturbance in prothionamide/ethionamide activation. | |||
Disease Class: Mycolicibacterium smegmatis infection | [3] | |||
Resistant Disease | Mycolicibacterium smegmatis infection [ICD-11: 1B2Z.6] | |||
Resistant Drug | Isoniazid | |||
Molecule Alteration | Missense mutation | p.G279V |
||
Experimental Note | Discovered Using In-vivo Testing Model | |||
In Vitro Model | Mycobacterium tuberculosis strain H37Rv ATCC27294 T | 83332 | ||
Experiment for Molecule Alteration |
Sequencing analysis | |||
Experiment for Drug Resistance |
In vitro drug susceptibility testing | |||
Mechanism Description | Notably, isoniazid is activated by the enzyme catalase-peroxidase, KatG, encoded by katG, whereas prothionamide is activated by the flavin monoxygenase, EthA, encoded by ethA. Mutations in katG and ethA are associated with individual isoniazid and prothionamide/ethionamide resistance, respectively. The ndh gene coding for NADH dehydrogenase, Ndh, was first identified as a new mechanism for INHR in Mycobacterium smegmatis. The mutations in ndh gene cause defects in the oxidation of NADH to NAD, which results in NADH accumulation and NAD depletion. The increased level of NADH inhibits the binding of isoniazid-NAD adduct to the active site of the InhA enzyme, which disturbs the regulation of enzyme activity and may cause co-resistance to isoniazid and prothionamide. EthR, a member of the TetR/CamR family, is a repressor of ethA. EthR regulates the transcription of ethA by coordinated octamerization on a 55-bp operator situated in the ethA-R intergenic region. Impeding EthR function leads to enhanced mycobacterial sensitivity to prothionamide, whereas mutations in ethR encoding a negative transcriptional regulator of the expression of EthA lead to prothionamide resistance. Finally, MshA, a member of the glycosyltransferase family, is a key enzyme involved in mycothiol biosynthesis in M. tuberculosis. Mutations in mshA coding MshA have been proposed to create a disturbance in prothionamide/ethionamide activation. | |||
Disease Class: Mycolicibacterium smegmatis infection | [3] | |||
Resistant Disease | Mycolicibacterium smegmatis infection [ICD-11: 1B2Z.6] | |||
Resistant Drug | Isoniazid | |||
Molecule Alteration | Missense mutation | p.L436P |
||
Experimental Note | Discovered Using In-vivo Testing Model | |||
In Vitro Model | Mycobacterium tuberculosis strain H37Rv ATCC27294 T | 83332 | ||
Experiment for Molecule Alteration |
Sequencing analysis | |||
Experiment for Drug Resistance |
In vitro drug susceptibility testing | |||
Mechanism Description | Notably, isoniazid is activated by the enzyme catalase-peroxidase, KatG, encoded by katG, whereas prothionamide is activated by the flavin monoxygenase, EthA, encoded by ethA. Mutations in katG and ethA are associated with individual isoniazid and prothionamide/ethionamide resistance, respectively. The ndh gene coding for NADH dehydrogenase, Ndh, was first identified as a new mechanism for INHR in Mycobacterium smegmatis. The mutations in ndh gene cause defects in the oxidation of NADH to NAD, which results in NADH accumulation and NAD depletion. The increased level of NADH inhibits the binding of isoniazid-NAD adduct to the active site of the InhA enzyme, which disturbs the regulation of enzyme activity and may cause co-resistance to isoniazid and prothionamide. EthR, a member of the TetR/CamR family, is a repressor of ethA. EthR regulates the transcription of ethA by coordinated octamerization on a 55-bp operator situated in the ethA-R intergenic region. Impeding EthR function leads to enhanced mycobacterial sensitivity to prothionamide, whereas mutations in ethR encoding a negative transcriptional regulator of the expression of EthA lead to prothionamide resistance. Finally, MshA, a member of the glycosyltransferase family, is a key enzyme involved in mycothiol biosynthesis in M. tuberculosis. Mutations in mshA coding MshA have been proposed to create a disturbance in prothionamide/ethionamide activation. | |||
Disease Class: Mycolicibacterium smegmatis infection | [3] | |||
Resistant Disease | Mycolicibacterium smegmatis infection [ICD-11: 1B2Z.6] | |||
Resistant Drug | Isoniazid | |||
Molecule Alteration | Missense mutation | p.N508D |
||
Experimental Note | Discovered Using In-vivo Testing Model | |||
In Vitro Model | Mycobacterium tuberculosis strain H37Rv ATCC27294 T | 83332 | ||
Experiment for Molecule Alteration |
Sequencing analysis | |||
Experiment for Drug Resistance |
In vitro drug susceptibility testing | |||
Mechanism Description | Notably, isoniazid is activated by the enzyme catalase-peroxidase, KatG, encoded by katG, whereas prothionamide is activated by the flavin monoxygenase, EthA, encoded by ethA. Mutations in katG and ethA are associated with individual isoniazid and prothionamide/ethionamide resistance, respectively. The ndh gene coding for NADH dehydrogenase, Ndh, was first identified as a new mechanism for INHR in Mycobacterium smegmatis. The mutations in ndh gene cause defects in the oxidation of NADH to NAD, which results in NADH accumulation and NAD depletion. The increased level of NADH inhibits the binding of isoniazid-NAD adduct to the active site of the InhA enzyme, which disturbs the regulation of enzyme activity and may cause co-resistance to isoniazid and prothionamide. EthR, a member of the TetR/CamR family, is a repressor of ethA. EthR regulates the transcription of ethA by coordinated octamerization on a 55-bp operator situated in the ethA-R intergenic region. Impeding EthR function leads to enhanced mycobacterial sensitivity to prothionamide, whereas mutations in ethR encoding a negative transcriptional regulator of the expression of EthA lead to prothionamide resistance. Finally, MshA, a member of the glycosyltransferase family, is a key enzyme involved in mycothiol biosynthesis in M. tuberculosis. Mutations in mshA coding MshA have been proposed to create a disturbance in prothionamide/ethionamide activation. | |||
Disease Class: Mycolicibacterium smegmatis infection | [3] | |||
Resistant Disease | Mycolicibacterium smegmatis infection [ICD-11: 1B2Z.6] | |||
Resistant Drug | Isoniazid | |||
Molecule Alteration | Missense mutation | p.P92S |
||
Experimental Note | Discovered Using In-vivo Testing Model | |||
In Vitro Model | Mycobacterium tuberculosis strain H37Rv ATCC27294 T | 83332 | ||
Experiment for Molecule Alteration |
Sequencing analysis | |||
Experiment for Drug Resistance |
In vitro drug susceptibility testing | |||
Mechanism Description | Notably, isoniazid is activated by the enzyme catalase-peroxidase, KatG, encoded by katG, whereas prothionamide is activated by the flavin monoxygenase, EthA, encoded by ethA. Mutations in katG and ethA are associated with individual isoniazid and prothionamide/ethionamide resistance, respectively. The ndh gene coding for NADH dehydrogenase, Ndh, was first identified as a new mechanism for INHR in Mycobacterium smegmatis. The mutations in ndh gene cause defects in the oxidation of NADH to NAD, which results in NADH accumulation and NAD depletion. The increased level of NADH inhibits the binding of isoniazid-NAD adduct to the active site of the InhA enzyme, which disturbs the regulation of enzyme activity and may cause co-resistance to isoniazid and prothionamide. EthR, a member of the TetR/CamR family, is a repressor of ethA. EthR regulates the transcription of ethA by coordinated octamerization on a 55-bp operator situated in the ethA-R intergenic region. Impeding EthR function leads to enhanced mycobacterial sensitivity to prothionamide, whereas mutations in ethR encoding a negative transcriptional regulator of the expression of EthA lead to prothionamide resistance. Finally, MshA, a member of the glycosyltransferase family, is a key enzyme involved in mycothiol biosynthesis in M. tuberculosis. Mutations in mshA coding MshA have been proposed to create a disturbance in prothionamide/ethionamide activation. | |||
Disease Class: Mycolicibacterium smegmatis infection | [3] | |||
Resistant Disease | Mycolicibacterium smegmatis infection [ICD-11: 1B2Z.6] | |||
Resistant Drug | Isoniazid | |||
Molecule Alteration | Missense mutation | p.S315T |
||
Experimental Note | Discovered Using In-vivo Testing Model | |||
In Vitro Model | Mycobacterium tuberculosis strain H37Rv ATCC27294 T | 83332 | ||
Experiment for Molecule Alteration |
Sequencing analysis | |||
Experiment for Drug Resistance |
In vitro drug susceptibility testing | |||
Mechanism Description | Notably, isoniazid is activated by the enzyme catalase-peroxidase, KatG, encoded by katG, whereas prothionamide is activated by the flavin monoxygenase, EthA, encoded by ethA. Mutations in katG and ethA are associated with individual isoniazid and prothionamide/ethionamide resistance, respectively. The ndh gene coding for NADH dehydrogenase, Ndh, was first identified as a new mechanism for INHR in Mycobacterium smegmatis. The mutations in ndh gene cause defects in the oxidation of NADH to NAD, which results in NADH accumulation and NAD depletion. The increased level of NADH inhibits the binding of isoniazid-NAD adduct to the active site of the InhA enzyme, which disturbs the regulation of enzyme activity and may cause co-resistance to isoniazid and prothionamide. EthR, a member of the TetR/CamR family, is a repressor of ethA. EthR regulates the transcription of ethA by coordinated octamerization on a 55-bp operator situated in the ethA-R intergenic region. Impeding EthR function leads to enhanced mycobacterial sensitivity to prothionamide, whereas mutations in ethR encoding a negative transcriptional regulator of the expression of EthA lead to prothionamide resistance. Finally, MshA, a member of the glycosyltransferase family, is a key enzyme involved in mycothiol biosynthesis in M. tuberculosis. Mutations in mshA coding MshA have been proposed to create a disturbance in prothionamide/ethionamide activation. | |||
Disease Class: Mycolicibacterium smegmatis infection | [3] | |||
Resistant Disease | Mycolicibacterium smegmatis infection [ICD-11: 1B2Z.6] | |||
Resistant Drug | Isoniazid | |||
Molecule Alteration | Missense mutation | p.G125S |
||
Experimental Note | Discovered Using In-vivo Testing Model | |||
In Vitro Model | Mycobacterium tuberculosis strain H37Rv ATCC27294 T | 83332 | ||
Experiment for Molecule Alteration |
Sequencing analysis | |||
Experiment for Drug Resistance |
In vitro drug susceptibility testing | |||
Mechanism Description | Notably, isoniazid is activated by the enzyme catalase-peroxidase, KatG, encoded by katG, whereas prothionamide is activated by the flavin monoxygenase, EthA, encoded by ethA. Mutations in katG and ethA are associated with individual isoniazid and prothionamide/ethionamide resistance, respectively. The ndh gene coding for NADH dehydrogenase, Ndh, was first identified as a new mechanism for INHR in Mycobacterium smegmatis. The mutations in ndh gene cause defects in the oxidation of NADH to NAD, which results in NADH accumulation and NAD depletion. The increased level of NADH inhibits the binding of isoniazid-NAD adduct to the active site of the InhA enzyme, which disturbs the regulation of enzyme activity and may cause co-resistance to isoniazid and prothionamide. EthR, a member of the TetR/CamR family, is a repressor of ethA. EthR regulates the transcription of ethA by coordinated octamerization on a 55-bp operator situated in the ethA-R intergenic region. Impeding EthR function leads to enhanced mycobacterial sensitivity to prothionamide, whereas mutations in ethR encoding a negative transcriptional regulator of the expression of EthA lead to prothionamide resistance. Finally, MshA, a member of the glycosyltransferase family, is a key enzyme involved in mycothiol biosynthesis in M. tuberculosis. Mutations in mshA coding MshA have been proposed to create a disturbance in prothionamide/ethionamide activation. | |||
Disease Class: Mycolicibacterium smegmatis infection | [3] | |||
Resistant Disease | Mycolicibacterium smegmatis infection [ICD-11: 1B2Z.6] | |||
Resistant Drug | Isoniazid | |||
Molecule Alteration | Missense mutation | p.Q127P |
||
Experimental Note | Discovered Using In-vivo Testing Model | |||
In Vitro Model | Mycobacterium tuberculosis strain H37Rv ATCC27294 T | 83332 | ||
Experiment for Molecule Alteration |
Sequencing analysis | |||
Experiment for Drug Resistance |
In vitro drug susceptibility testing | |||
Mechanism Description | Notably, isoniazid is activated by the enzyme catalase-peroxidase, KatG, encoded by katG, whereas prothionamide is activated by the flavin monoxygenase, EthA, encoded by ethA. Mutations in katG and ethA are associated with individual isoniazid and prothionamide/ethionamide resistance, respectively. The ndh gene coding for NADH dehydrogenase, Ndh, was first identified as a new mechanism for INHR in Mycobacterium smegmatis. The mutations in ndh gene cause defects in the oxidation of NADH to NAD, which results in NADH accumulation and NAD depletion. The increased level of NADH inhibits the binding of isoniazid-NAD adduct to the active site of the InhA enzyme, which disturbs the regulation of enzyme activity and may cause co-resistance to isoniazid and prothionamide. EthR, a member of the TetR/CamR family, is a repressor of ethA. EthR regulates the transcription of ethA by coordinated octamerization on a 55-bp operator situated in the ethA-R intergenic region. Impeding EthR function leads to enhanced mycobacterial sensitivity to prothionamide, whereas mutations in ethR encoding a negative transcriptional regulator of the expression of EthA lead to prothionamide resistance. Finally, MshA, a member of the glycosyltransferase family, is a key enzyme involved in mycothiol biosynthesis in M. tuberculosis. Mutations in mshA coding MshA have been proposed to create a disturbance in prothionamide/ethionamide activation. | |||
Disease Class: Mycolicibacterium smegmatis infection | [3] | |||
Resistant Disease | Mycolicibacterium smegmatis infection [ICD-11: 1B2Z.6] | |||
Resistant Drug | Isoniazid | |||
Molecule Alteration | Missense mutation | p.V431A |
||
Experimental Note | Discovered Using In-vivo Testing Model | |||
In Vitro Model | Mycobacterium tuberculosis strain H37Rv ATCC27294 T | 83332 | ||
Experiment for Molecule Alteration |
Sequencing analysis | |||
Experiment for Drug Resistance |
In vitro drug susceptibility testing | |||
Mechanism Description | Notably, isoniazid is activated by the enzyme catalase-peroxidase, KatG, encoded by katG, whereas prothionamide is activated by the flavin monoxygenase, EthA, encoded by ethA. Mutations in katG and ethA are associated with individual isoniazid and prothionamide/ethionamide resistance, respectively. The ndh gene coding for NADH dehydrogenase, Ndh, was first identified as a new mechanism for INHR in Mycobacterium smegmatis. The mutations in ndh gene cause defects in the oxidation of NADH to NAD, which results in NADH accumulation and NAD depletion. The increased level of NADH inhibits the binding of isoniazid-NAD adduct to the active site of the InhA enzyme, which disturbs the regulation of enzyme activity and may cause co-resistance to isoniazid and prothionamide. EthR, a member of the TetR/CamR family, is a repressor of ethA. EthR regulates the transcription of ethA by coordinated octamerization on a 55-bp operator situated in the ethA-R intergenic region. Impeding EthR function leads to enhanced mycobacterial sensitivity to prothionamide, whereas mutations in ethR encoding a negative transcriptional regulator of the expression of EthA lead to prothionamide resistance. Finally, MshA, a member of the glycosyltransferase family, is a key enzyme involved in mycothiol biosynthesis in M. tuberculosis. Mutations in mshA coding MshA have been proposed to create a disturbance in prothionamide/ethionamide activation. | |||
Disease Class: Mycolicibacterium smegmatis infection | [3] | |||
Resistant Disease | Mycolicibacterium smegmatis infection [ICD-11: 1B2Z.6] | |||
Resistant Drug | Isoniazid | |||
Molecule Alteration | Missense mutation | p.G490S |
||
Experimental Note | Discovered Using In-vivo Testing Model | |||
In Vitro Model | Mycobacterium tuberculosis strain H37Rv ATCC27294 T | 83332 | ||
Experiment for Molecule Alteration |
Sequencing analysis | |||
Experiment for Drug Resistance |
In vitro drug susceptibility testing | |||
Mechanism Description | Notably, isoniazid is activated by the enzyme catalase-peroxidase, KatG, encoded by katG, whereas prothionamide is activated by the flavin monoxygenase, EthA, encoded by ethA. Mutations in katG and ethA are associated with individual isoniazid and prothionamide/ethionamide resistance, respectively. The ndh gene coding for NADH dehydrogenase, Ndh, was first identified as a new mechanism for INHR in Mycobacterium smegmatis. The mutations in ndh gene cause defects in the oxidation of NADH to NAD, which results in NADH accumulation and NAD depletion. The increased level of NADH inhibits the binding of isoniazid-NAD adduct to the active site of the InhA enzyme, which disturbs the regulation of enzyme activity and may cause co-resistance to isoniazid and prothionamide. EthR, a member of the TetR/CamR family, is a repressor of ethA. EthR regulates the transcription of ethA by coordinated octamerization on a 55-bp operator situated in the ethA-R intergenic region. Impeding EthR function leads to enhanced mycobacterial sensitivity to prothionamide, whereas mutations in ethR encoding a negative transcriptional regulator of the expression of EthA lead to prothionamide resistance. Finally, MshA, a member of the glycosyltransferase family, is a key enzyme involved in mycothiol biosynthesis in M. tuberculosis. Mutations in mshA coding MshA have been proposed to create a disturbance in prothionamide/ethionamide activation. | |||
Disease Class: Mycolicibacterium smegmatis infection | [3] | |||
Resistant Disease | Mycolicibacterium smegmatis infection [ICD-11: 1B2Z.6] | |||
Resistant Drug | Isoniazid | |||
Molecule Alteration | Missense mutation | p.Q461P |
||
Experimental Note | Discovered Using In-vivo Testing Model | |||
In Vitro Model | Mycobacterium tuberculosis strain H37Rv ATCC27294 T | 83332 | ||
Experiment for Molecule Alteration |
Sequencing analysis | |||
Experiment for Drug Resistance |
In vitro drug susceptibility testing | |||
Mechanism Description | Notably, isoniazid is activated by the enzyme catalase-peroxidase, KatG, encoded by katG, whereas prothionamide is activated by the flavin monoxygenase, EthA, encoded by ethA. Mutations in katG and ethA are associated with individual isoniazid and prothionamide/ethionamide resistance, respectively. The ndh gene coding for NADH dehydrogenase, Ndh, was first identified as a new mechanism for INHR in Mycobacterium smegmatis. The mutations in ndh gene cause defects in the oxidation of NADH to NAD, which results in NADH accumulation and NAD depletion. The increased level of NADH inhibits the binding of isoniazid-NAD adduct to the active site of the InhA enzyme, which disturbs the regulation of enzyme activity and may cause co-resistance to isoniazid and prothionamide. EthR, a member of the TetR/CamR family, is a repressor of ethA. EthR regulates the transcription of ethA by coordinated octamerization on a 55-bp operator situated in the ethA-R intergenic region. Impeding EthR function leads to enhanced mycobacterial sensitivity to prothionamide, whereas mutations in ethR encoding a negative transcriptional regulator of the expression of EthA lead to prothionamide resistance. Finally, MshA, a member of the glycosyltransferase family, is a key enzyme involved in mycothiol biosynthesis in M. tuberculosis. Mutations in mshA coding MshA have been proposed to create a disturbance in prothionamide/ethionamide activation. | |||
Disease Class: Mycolicibacterium smegmatis infection | [3] | |||
Resistant Disease | Mycolicibacterium smegmatis infection [ICD-11: 1B2Z.6] | |||
Resistant Drug | Isoniazid | |||
Molecule Alteration | Missense mutation | p.E607A |
||
Experimental Note | Discovered Using In-vivo Testing Model | |||
In Vitro Model | Mycobacterium tuberculosis strain H37Rv ATCC27294 T | 83332 | ||
Experiment for Molecule Alteration |
Sequencing analysis | |||
Experiment for Drug Resistance |
In vitro drug susceptibility testing | |||
Mechanism Description | Notably, isoniazid is activated by the enzyme catalase-peroxidase, KatG, encoded by katG, whereas prothionamide is activated by the flavin monoxygenase, EthA, encoded by ethA. Mutations in katG and ethA are associated with individual isoniazid and prothionamide/ethionamide resistance, respectively. The ndh gene coding for NADH dehydrogenase, Ndh, was first identified as a new mechanism for INHR in Mycobacterium smegmatis. The mutations in ndh gene cause defects in the oxidation of NADH to NAD, which results in NADH accumulation and NAD depletion. The increased level of NADH inhibits the binding of isoniazid-NAD adduct to the active site of the InhA enzyme, which disturbs the regulation of enzyme activity and may cause co-resistance to isoniazid and prothionamide. EthR, a member of the TetR/CamR family, is a repressor of ethA. EthR regulates the transcription of ethA by coordinated octamerization on a 55-bp operator situated in the ethA-R intergenic region. Impeding EthR function leads to enhanced mycobacterial sensitivity to prothionamide, whereas mutations in ethR encoding a negative transcriptional regulator of the expression of EthA lead to prothionamide resistance. Finally, MshA, a member of the glycosyltransferase family, is a key enzyme involved in mycothiol biosynthesis in M. tuberculosis. Mutations in mshA coding MshA have been proposed to create a disturbance in prothionamide/ethionamide activation. | |||
Disease Class: Mycolicibacterium smegmatis infection | [3] | |||
Resistant Disease | Mycolicibacterium smegmatis infection [ICD-11: 1B2Z.6] | |||
Resistant Drug | Isoniazid | |||
Molecule Alteration | Missense mutation | p.H417Q |
||
Experimental Note | Discovered Using In-vivo Testing Model | |||
In Vitro Model | Mycobacterium tuberculosis strain H37Rv ATCC27294 T | 83332 | ||
Experiment for Molecule Alteration |
Sequencing analysis | |||
Experiment for Drug Resistance |
In vitro drug susceptibility testing | |||
Mechanism Description | Notably, isoniazid is activated by the enzyme catalase-peroxidase, KatG, encoded by katG, whereas prothionamide is activated by the flavin monoxygenase, EthA, encoded by ethA. Mutations in katG and ethA are associated with individual isoniazid and prothionamide/ethionamide resistance, respectively. The ndh gene coding for NADH dehydrogenase, Ndh, was first identified as a new mechanism for INHR in Mycobacterium smegmatis. The mutations in ndh gene cause defects in the oxidation of NADH to NAD, which results in NADH accumulation and NAD depletion. The increased level of NADH inhibits the binding of isoniazid-NAD adduct to the active site of the InhA enzyme, which disturbs the regulation of enzyme activity and may cause co-resistance to isoniazid and prothionamide. EthR, a member of the TetR/CamR family, is a repressor of ethA. EthR regulates the transcription of ethA by coordinated octamerization on a 55-bp operator situated in the ethA-R intergenic region. Impeding EthR function leads to enhanced mycobacterial sensitivity to prothionamide, whereas mutations in ethR encoding a negative transcriptional regulator of the expression of EthA lead to prothionamide resistance. Finally, MshA, a member of the glycosyltransferase family, is a key enzyme involved in mycothiol biosynthesis in M. tuberculosis. Mutations in mshA coding MshA have been proposed to create a disturbance in prothionamide/ethionamide activation. | |||
Disease Class: Mycolicibacterium smegmatis infection | [3] | |||
Resistant Disease | Mycolicibacterium smegmatis infection [ICD-11: 1B2Z.6] | |||
Resistant Drug | Isoniazid | |||
Molecule Alteration | Missense mutation | p.G111S |
||
Experimental Note | Discovered Using In-vivo Testing Model | |||
In Vitro Model | Mycobacterium tuberculosis strain H37Rv ATCC27294 T | 83332 | ||
Experiment for Molecule Alteration |
Sequencing analysis | |||
Experiment for Drug Resistance |
In vitro drug susceptibility testing | |||
Mechanism Description | Notably, isoniazid is activated by the enzyme catalase-peroxidase, KatG, encoded by katG, whereas prothionamide is activated by the flavin monoxygenase, EthA, encoded by ethA. Mutations in katG and ethA are associated with individual isoniazid and prothionamide/ethionamide resistance, respectively. The ndh gene coding for NADH dehydrogenase, Ndh, was first identified as a new mechanism for INHR in Mycobacterium smegmatis. The mutations in ndh gene cause defects in the oxidation of NADH to NAD, which results in NADH accumulation and NAD depletion. The increased level of NADH inhibits the binding of isoniazid-NAD adduct to the active site of the InhA enzyme, which disturbs the regulation of enzyme activity and may cause co-resistance to isoniazid and prothionamide. EthR, a member of the TetR/CamR family, is a repressor of ethA. EthR regulates the transcription of ethA by coordinated octamerization on a 55-bp operator situated in the ethA-R intergenic region. Impeding EthR function leads to enhanced mycobacterial sensitivity to prothionamide, whereas mutations in ethR encoding a negative transcriptional regulator of the expression of EthA lead to prothionamide resistance. Finally, MshA, a member of the glycosyltransferase family, is a key enzyme involved in mycothiol biosynthesis in M. tuberculosis. Mutations in mshA coding MshA have been proposed to create a disturbance in prothionamide/ethionamide activation. | |||
Disease Class: Mycolicibacterium smegmatis infection | [3] | |||
Resistant Disease | Mycolicibacterium smegmatis infection [ICD-11: 1B2Z.6] | |||
Resistant Drug | Isoniazid | |||
Molecule Alteration | Missense mutation | p.G33V |
||
Experimental Note | Discovered Using In-vivo Testing Model | |||
In Vitro Model | Mycobacterium tuberculosis strain H37Rv ATCC27294 T | 83332 | ||
Experiment for Molecule Alteration |
Sequencing analysis | |||
Experiment for Drug Resistance |
In vitro drug susceptibility testing | |||
Mechanism Description | Notably, isoniazid is activated by the enzyme catalase-peroxidase, KatG, encoded by katG, whereas prothionamide is activated by the flavin monoxygenase, EthA, encoded by ethA. Mutations in katG and ethA are associated with individual isoniazid and prothionamide/ethionamide resistance, respectively. The ndh gene coding for NADH dehydrogenase, Ndh, was first identified as a new mechanism for INHR in Mycobacterium smegmatis. The mutations in ndh gene cause defects in the oxidation of NADH to NAD, which results in NADH accumulation and NAD depletion. The increased level of NADH inhibits the binding of isoniazid-NAD adduct to the active site of the InhA enzyme, which disturbs the regulation of enzyme activity and may cause co-resistance to isoniazid and prothionamide. EthR, a member of the TetR/CamR family, is a repressor of ethA. EthR regulates the transcription of ethA by coordinated octamerization on a 55-bp operator situated in the ethA-R intergenic region. Impeding EthR function leads to enhanced mycobacterial sensitivity to prothionamide, whereas mutations in ethR encoding a negative transcriptional regulator of the expression of EthA lead to prothionamide resistance. Finally, MshA, a member of the glycosyltransferase family, is a key enzyme involved in mycothiol biosynthesis in M. tuberculosis. Mutations in mshA coding MshA have been proposed to create a disturbance in prothionamide/ethionamide activation. | |||
Disease Class: Mycolicibacterium smegmatis infection | [3] | |||
Resistant Disease | Mycolicibacterium smegmatis infection [ICD-11: 1B2Z.6] | |||
Resistant Drug | Isoniazid | |||
Molecule Alteration | Missense mutation | p.W191R |
||
Experimental Note | Discovered Using In-vivo Testing Model | |||
In Vitro Model | Mycobacterium tuberculosis strain H37Rv ATCC27294 T | 83332 | ||
Experiment for Molecule Alteration |
Sequencing analysis | |||
Experiment for Drug Resistance |
In vitro drug susceptibility testing | |||
Mechanism Description | Notably, isoniazid is activated by the enzyme catalase-peroxidase, KatG, encoded by katG, whereas prothionamide is activated by the flavin monoxygenase, EthA, encoded by ethA. Mutations in katG and ethA are associated with individual isoniazid and prothionamide/ethionamide resistance, respectively. The ndh gene coding for NADH dehydrogenase, Ndh, was first identified as a new mechanism for INHR in Mycobacterium smegmatis. The mutations in ndh gene cause defects in the oxidation of NADH to NAD, which results in NADH accumulation and NAD depletion. The increased level of NADH inhibits the binding of isoniazid-NAD adduct to the active site of the InhA enzyme, which disturbs the regulation of enzyme activity and may cause co-resistance to isoniazid and prothionamide. EthR, a member of the TetR/CamR family, is a repressor of ethA. EthR regulates the transcription of ethA by coordinated octamerization on a 55-bp operator situated in the ethA-R intergenic region. Impeding EthR function leads to enhanced mycobacterial sensitivity to prothionamide, whereas mutations in ethR encoding a negative transcriptional regulator of the expression of EthA lead to prothionamide resistance. Finally, MshA, a member of the glycosyltransferase family, is a key enzyme involved in mycothiol biosynthesis in M. tuberculosis. Mutations in mshA coding MshA have been proposed to create a disturbance in prothionamide/ethionamide activation. | |||
Unusual Activation of Pro-survival Pathway (UAPP) | ||||
Disease Class: Urinary tuberculosis | [4] | |||
Resistant Disease | Urinary tuberculosis [ICD-11: 1G80.0] | |||
Resistant Drug | Isoniazid | |||
Molecule Alteration | Missense mutation | p.S531L |
||
Experimental Note | Identified from the Human Clinical Data | |||
In Vitro Model | Mycobacterium tuberculosis isolates | 1773 | ||
Experiment for Molecule Alteration |
Gene sequencing assay | |||
Mechanism Description | Regarding drug-resistance mutation profiles, the most prevalent mutation sites were katG S315T1 and rpoB S531L. | |||
Disease Class: Urinary tuberculosis | [4] | |||
Resistant Disease | Urinary tuberculosis [ICD-11: 1G80.0] | |||
Resistant Drug | Isoniazid | |||
Molecule Alteration | Missense mutation | p.S315T1 |
||
Experimental Note | Identified from the Human Clinical Data | |||
In Vitro Model | Mycobacterium tuberculosis isolates | 1773 | ||
Experiment for Molecule Alteration |
Gene sequencing assay | |||
Mechanism Description | Regarding drug-resistance mutation profiles, the most prevalent mutation sites were katG S315T1 and rpoB S531L. |
Rifampin
Drug Resistance Data Categorized by Their Corresponding Mechanisms | ||||
Unusual Activation of Pro-survival Pathway (UAPP) | ||||
Disease Class: Urinary tuberculosis | [4] | |||
Resistant Disease | Urinary tuberculosis [ICD-11: 1G80.0] | |||
Resistant Drug | Rifampin | |||
Molecule Alteration | Missense mutation | p.S531L |
||
Experimental Note | Identified from the Human Clinical Data | |||
In Vitro Model | Mycobacterium tuberculosis isolates | 1773 | ||
Experiment for Molecule Alteration |
Gene sequencing assay | |||
Mechanism Description | Regarding drug-resistance mutation profiles, the most prevalent mutation sites were katG S315T1 and rpoB S531L. | |||
Disease Class: Urinary tuberculosis | [4] | |||
Resistant Disease | Urinary tuberculosis [ICD-11: 1G80.0] | |||
Resistant Drug | Rifampin | |||
Molecule Alteration | Missense mutation | p.S315T1 |
||
Experimental Note | Identified from the Human Clinical Data | |||
In Vitro Model | Mycobacterium tuberculosis isolates | 1773 | ||
Experiment for Molecule Alteration |
Gene sequencing assay | |||
Mechanism Description | Regarding drug-resistance mutation profiles, the most prevalent mutation sites were katG S315T1 and rpoB S531L. |
References
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