Disease Information

General Information of the Disease (ID: DIS00032)

• Name: Bacillus infection
• ICD: ICD-11: 1C4Y

Type(s) of Resistant Mechanism of This Disease

  ADTT: Aberration of the Drug's Therapeutic Target

  DISM: Drug Inactivation by Structure Modification

  IDUE: Irregularity in Drug Uptake and Drug Efflux

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

Approved Drug(s) 19 drug(s) in total

Bacitracin A

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Bacitracin transport permease protein BCRB (BCRB) [1]

• Resistant Disease: Bacillus licheniformis infection [ICD-11: 1C4Y.2]
• Molecule Alteration: Expression; Inherence
• Resistant Drug: Bacitracin A
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Escherichia coli strain HB101; 634468
• In Vitro Model: Escherichia coli strain DH5alpha; 668369
• In Vitro Model: Bacillus subtilis strain 1A685; 1423
• In Vitro Model: Bacillus subtilis strain vectors pHV143; 1423
• In Vitro Model: Bacillus ticheniformis strain FD; 1402
• Experiment for Molecule Alteration: Dideoxynucleotide chain-termination method assay
• Experiment for Drug Resistance: MIC assay
• Mechanism Description: How could the proposed export function of the Bcr permease account for the bacitracin resistance The transported molecule could be either the substance inactivating the antibiotic or the antibiotic alone. As already observed. some of the metabolites could inhibit the bactericidal activity of bacitracin at very low concentrations. However, in S. subfitis and Escherichia coli strains carrying cloned bcr genes, no substances that could suppress bacitracin activity were detected. It seems that the bacitracin is indeed the target of the Bcr ABC transporter.

Key Molecule: Bacitracin transport ATP-binding protein BcrA (BCRA) [1]

• Resistant Disease: Bacillus licheniformis infection [ICD-11: 1C4Y.2]
• Molecule Alteration: Expression; Inherence
• Resistant Drug: Bacitracin A
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Escherichia coli strain HB101; 634468
• In Vitro Model: Escherichia coli strain DH5alpha; 668369
• In Vitro Model: Bacillus subtilis strain 1A685; 1423
• In Vitro Model: Bacillus subtilis strain vectors pHV143; 1423
• In Vitro Model: Bacillus ticheniformis strain FD; 1402
• Experiment for Molecule Alteration: Dideoxynucleotide chain-termination method assay
• Experiment for Drug Resistance: MIC assay
• Mechanism Description: How could the proposed export function of the Bcr permease account for the bacitracin resistance The transported molecule could be either the substance inactivating the antibiotic or the antibiotic alone. As already observed. some of the metabolites could inhibit the bactericidal activity of bacitracin at very low concentrations. However, in S. subfitis and Escherichia coli strains carrying cloned bcr genes, no substances that could suppress bacitracin activity were detected. It seems that the bacitracin is indeed the target of the Bcr ABC transporter.

Bacitracin F

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Bacitracin transport permease protein BCRB (BCRB) [1]

• Resistant Disease: Bacillus licheniformis infection [ICD-11: 1C4Y.2]
• Molecule Alteration: Expression; Inherence
• Resistant Drug: Bacitracin F
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Escherichia coli strain HB101; 634468
• In Vitro Model: Escherichia coli strain DH5alpha; 668369
• In Vitro Model: Bacillus subtilis strain 1A685; 1423
• In Vitro Model: Bacillus subtilis strain vectors pHV143; 1423
• In Vitro Model: Bacillus ticheniformis strain FD; 1402
• Experiment for Molecule Alteration: Dideoxynucleotide chain-termination method assay
• Experiment for Drug Resistance: MIC assay
• Mechanism Description: How could the proposed export function of the Bcr permease account for the bacitracin resistance The transported molecule could be either the substance inactivating the antibiotic or the antibiotic alone. As already observed. some of the metabolites could inhibit the bactericidal activity of bacitracin at very low concentrations. However, in S. subfitis and Escherichia coli strains carrying cloned bcr genes, no substances that could suppress bacitracin activity were detected. It seems that the bacitracin is indeed the target of the Bcr ABC transporter.

Key Molecule: Bacitracin transport ATP-binding protein BcrA (BCRA) [1]

• Resistant Disease: Bacillus licheniformis infection [ICD-11: 1C4Y.2]
• Molecule Alteration: Expression; Inherence
• Resistant Drug: Bacitracin F
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Escherichia coli strain HB101; 634468
• In Vitro Model: Escherichia coli strain DH5alpha; 668369
• In Vitro Model: Bacillus subtilis strain 1A685; 1423
• In Vitro Model: Bacillus subtilis strain vectors pHV143; 1423
• In Vitro Model: Bacillus ticheniformis strain FD; 1402
• Experiment for Molecule Alteration: Dideoxynucleotide chain-termination method assay
• Experiment for Drug Resistance: MIC assay
• Mechanism Description: How could the proposed export function of the Bcr permease account for the bacitracin resistance The transported molecule could be either the substance inactivating the antibiotic or the antibiotic alone. As already observed. some of the metabolites could inhibit the bactericidal activity of bacitracin at very low concentrations. However, in S. subfitis and Escherichia coli strains carrying cloned bcr genes, no substances that could suppress bacitracin activity were detected. It seems that the bacitracin is indeed the target of the Bcr ABC transporter.

Bacitracin methylene disalicylate

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Bacitracin transport permease protein BCRB (BCRB) [1]

• Resistant Disease: Bacillus licheniformis infection [ICD-11: 1C4Y.2]
• Molecule Alteration: Expression; Inherence
• Resistant Drug: Bacitracin methylene disalicylate
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Escherichia coli strain HB101; 634468
• In Vitro Model: Escherichia coli strain DH5alpha; 668369
• In Vitro Model: Bacillus subtilis strain 1A685; 1423
• In Vitro Model: Bacillus subtilis strain vectors pHV143; 1423
• In Vitro Model: Bacillus ticheniformis strain FD; 1402
• Experiment for Molecule Alteration: Dideoxynucleotide chain-termination method assay
• Experiment for Drug Resistance: MIC assay
• Mechanism Description: How could the proposed export function of the Bcr permease account for the bacitracin resistance The transported molecule could be either the substance inactivating the antibiotic or the antibiotic alone. As already observed. some of the metabolites could inhibit the bactericidal activity of bacitracin at very low concentrations. However, in S. subfitis and Escherichia coli strains carrying cloned bcr genes, no substances that could suppress bacitracin activity were detected. It seems that the bacitracin is indeed the target of the Bcr ABC transporter.

Key Molecule: Bacitracin transport ATP-binding protein BcrA (BCRA) [1]

• Resistant Disease: Bacillus licheniformis infection [ICD-11: 1C4Y.2]
• Molecule Alteration: Expression; Inherence
• Resistant Drug: Bacitracin methylene disalicylate
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Escherichia coli strain HB101; 634468
• In Vitro Model: Escherichia coli strain DH5alpha; 668369
• In Vitro Model: Bacillus subtilis strain 1A685; 1423
• In Vitro Model: Bacillus subtilis strain vectors pHV143; 1423
• In Vitro Model: Bacillus ticheniformis strain FD; 1402
• Experiment for Molecule Alteration: Dideoxynucleotide chain-termination method assay
• Experiment for Drug Resistance: MIC assay
• Mechanism Description: How could the proposed export function of the Bcr permease account for the bacitracin resistance The transported molecule could be either the substance inactivating the antibiotic or the antibiotic alone. As already observed. some of the metabolites could inhibit the bactericidal activity of bacitracin at very low concentrations. However, in S. subfitis and Escherichia coli strains carrying cloned bcr genes, no substances that could suppress bacitracin activity were detected. It seems that the bacitracin is indeed the target of the Bcr ABC transporter.

Cefoxitin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: ErmR rRNA adenine N6-methyltransferase (ERMR) [2]

• Resistant Disease: Bacteroides fragilis infection [ICD-11: 1C4Y.6]
• Molecule Alteration: Expression; Inherence
• Resistant Drug: Cefoxitin
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Bacteroides distasonis strains; 823
• In Vitro Model: Bacteroides distasonis strains V2002; 823
• In Vitro Model: Bacteroides distasonis strains V2003; 823
• In Vitro Model: Bacteroides distasonis strains V2004; 823
• In Vitro Model: Bacteroides fragilis strain; 817
• In Vitro Model: Bacteroides fragilis strain V503; 817
• In Vitro Model: Bacteroides ovatus strains; 28116
• In Vitro Model: Bacteroides ovatus strains V2008; 28116
• In Vitro Model: Bacteroides thetaiotaomicron strain; 818
• In Vitro Model: Bacteroides thetaiotaomicron strain V2005; 818
• In Vitro Model: Bacteroides thetaiotaomicron strain V2006; 818
• In Vitro Model: Bacteroides thetaiotaomicron strain V2007; 818
• In Vitro Model: Bacteroides uniformis strain; 820
• In Vitro Model: Bacteroides uniformis strain V1760; 820
• In Vitro Model: Bacteroides uniformis strain V1761; 820
• In Vitro Model: Bacteroides uniformis strain V1918; 820
• In Vitro Model: Bacteroides uniformis strain V1921; 820
• In Vitro Model: Bacteroides uniformis strain V2000; 820
• In Vitro Model: Bacteroides uniformis strain V2001; 820
• In Vitro Model: Bacteroides uniformis strain V528; 820
• In Vitro Model: Bacteroides uniformis strain V844; 820
• Experiment for Molecule Alteration: Southern blotting assay
• Mechanism Description: Clindamycin resistance in Bacteroides spp. is usually macrolide-lincosamide-streptogramin B (MLS) resistance conferred by erm genes which are similar to those seen in gram-positive, facultative anaerobes. Of 13 clinical isolates of the Bacteroides group, all were resistant to tetracycline (>10,ug/ml).

Key Molecule: ErmR rRNA adenine N6-methyltransferase (ERMR) [2]

• Resistant Disease: Bacteroides uniformis infection [ICD-11: 1C4Y.11]
• Molecule Alteration: Expression; Inherence
• Resistant Drug: Cefoxitin
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Bacteroides distasonis strains; 823
• In Vitro Model: Bacteroides distasonis strains V2002; 823
• In Vitro Model: Bacteroides distasonis strains V2003; 823
• In Vitro Model: Bacteroides distasonis strains V2004; 823
• In Vitro Model: Bacteroides fragilis strain; 817
• In Vitro Model: Bacteroides fragilis strain V503; 817
• In Vitro Model: Bacteroides ovatus strains; 28116
• In Vitro Model: Bacteroides ovatus strains V2008; 28116
• In Vitro Model: Bacteroides thetaiotaomicron strain; 818
• In Vitro Model: Bacteroides thetaiotaomicron strain V2005; 818
• In Vitro Model: Bacteroides thetaiotaomicron strain V2006; 818
• In Vitro Model: Bacteroides thetaiotaomicron strain V2007; 818
• In Vitro Model: Bacteroides uniformis strain; 820
• In Vitro Model: Bacteroides uniformis strain V1760; 820
• In Vitro Model: Bacteroides uniformis strain V1761; 820
• In Vitro Model: Bacteroides uniformis strain V1918; 820
• In Vitro Model: Bacteroides uniformis strain V1921; 820
• In Vitro Model: Bacteroides uniformis strain V2000; 820
• In Vitro Model: Bacteroides uniformis strain V2001; 820
• In Vitro Model: Bacteroides uniformis strain V528; 820
• In Vitro Model: Bacteroides uniformis strain V844; 820
• Experiment for Molecule Alteration: Southern blotting assay
• Mechanism Description: Clindamycin resistance in Bacteroides spp. is usually macrolide-lincosamide-streptogramin B (MLS) resistance conferred by erm genes which are similar to those seen in gram-positive, facultative anaerobes. Of 13 clinical isolates of the Bacteroides group, all were resistant to tetracycline (>10,ug/ml).

Key Molecule: ErmR rRNA adenine N6-methyltransferase (ERMR) [2]

• Resistant Disease: Bacteroides thetaiotaomicron infection [ICD-11: 1C4Y.10]
• Molecule Alteration: Expression; Inherence
• Resistant Drug: Cefoxitin
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Bacteroides distasonis strains; 823
• In Vitro Model: Bacteroides distasonis strains V2002; 823
• In Vitro Model: Bacteroides distasonis strains V2003; 823
• In Vitro Model: Bacteroides distasonis strains V2004; 823
• In Vitro Model: Bacteroides fragilis strain; 817
• In Vitro Model: Bacteroides fragilis strain V503; 817
• In Vitro Model: Bacteroides ovatus strains; 28116
• In Vitro Model: Bacteroides ovatus strains V2008; 28116
• In Vitro Model: Bacteroides thetaiotaomicron strain; 818
• In Vitro Model: Bacteroides thetaiotaomicron strain V2005; 818
• In Vitro Model: Bacteroides thetaiotaomicron strain V2006; 818
• In Vitro Model: Bacteroides thetaiotaomicron strain V2007; 818
• In Vitro Model: Bacteroides uniformis strain; 820
• In Vitro Model: Bacteroides uniformis strain V1760; 820
• In Vitro Model: Bacteroides uniformis strain V1761; 820
• In Vitro Model: Bacteroides uniformis strain V1918; 820
• In Vitro Model: Bacteroides uniformis strain V1921; 820
• In Vitro Model: Bacteroides uniformis strain V2000; 820
• In Vitro Model: Bacteroides uniformis strain V2001; 820
• In Vitro Model: Bacteroides uniformis strain V528; 820
• In Vitro Model: Bacteroides uniformis strain V844; 820
• Experiment for Molecule Alteration: Southern blotting assay
• Mechanism Description: Clindamycin resistance in Bacteroides spp. is usually macrolide-lincosamide-streptogramin B (MLS) resistance conferred by erm genes which are similar to those seen in gram-positive, facultative anaerobes. Of 13 clinical isolates of the Bacteroides group, all were resistant to tetracycline (>10,ug/ml).

Key Molecule: ErmR rRNA adenine N6-methyltransferase (ERMR) [2]

• Resistant Disease: Bacteroides ovatus infection [ICD-11: 1C4Y.8]
• Molecule Alteration: Expression; Inherence
• Resistant Drug: Cefoxitin
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Bacteroides distasonis strains; 823
• In Vitro Model: Bacteroides distasonis strains V2002; 823
• In Vitro Model: Bacteroides distasonis strains V2003; 823
• In Vitro Model: Bacteroides distasonis strains V2004; 823
• In Vitro Model: Bacteroides fragilis strain; 817
• In Vitro Model: Bacteroides fragilis strain V503; 817
• In Vitro Model: Bacteroides ovatus strains; 28116
• In Vitro Model: Bacteroides ovatus strains V2008; 28116
• In Vitro Model: Bacteroides thetaiotaomicron strain; 818
• In Vitro Model: Bacteroides thetaiotaomicron strain V2005; 818
• In Vitro Model: Bacteroides thetaiotaomicron strain V2006; 818
• In Vitro Model: Bacteroides thetaiotaomicron strain V2007; 818
• In Vitro Model: Bacteroides uniformis strain; 820
• In Vitro Model: Bacteroides uniformis strain V1760; 820
• In Vitro Model: Bacteroides uniformis strain V1761; 820
• In Vitro Model: Bacteroides uniformis strain V1918; 820
• In Vitro Model: Bacteroides uniformis strain V1921; 820
• In Vitro Model: Bacteroides uniformis strain V2000; 820
• In Vitro Model: Bacteroides uniformis strain V2001; 820
• In Vitro Model: Bacteroides uniformis strain V528; 820
• In Vitro Model: Bacteroides uniformis strain V844; 820
• Experiment for Molecule Alteration: Southern blotting assay
• Mechanism Description: Clindamycin resistance in Bacteroides spp. is usually macrolide-lincosamide-streptogramin B (MLS) resistance conferred by erm genes which are similar to those seen in gram-positive, facultative anaerobes. Of 13 clinical isolates of the Bacteroides group, all were resistant to tetracycline (>10,ug/ml). Seven of the eight clindamycin-resistant clinical isolates constitutively expressed erythromycin resistance and had a high level of resistance to clindamycin (> 10ug/ml). V2002 was susceptible to erythromycin.

Drug Inactivation by Structure Modification (DISM)

Key Molecule: Beta-lactamase (BLA) [3]

• Resistant Disease: Bacteroides infection [ICD-11: 1C4Y.7]
• Molecule Alteration: Expression; Inherence
• Resistant Drug: Cefoxitin
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli strain HB101; 634468
• In Vitro Model: Escherichia coli strain DH5a; 668369
• In Vitro Model: Bacteroides uniformis strain V528; 820
• In Vitro Model: Bacteroides fragilis strain 638; 862962
• In Vitro Model: Bacteroides fragilis strain IB246; 817
• In Vitro Model: Bacteroides fragilis strain IB246flpSUC2C; 817
• In Vitro Model: Bacteroides fragilis strain IB247; 817
• In Vitro Model: Bacteroides vulgatus strain CLA341; 821
• Experiment for Molecule Alteration: Nucleotide sequence assay
• Experiment for Drug Resistance: Standard broth microdilution method assay
• Mechanism Description: The beta-lactamase gene (cfxA) was subcloned on a 2.2-kb DraI-HindIII fragment, and the nucleotide sequence was determined. These results showed that cfxA encoded a protein of 321 amino acids and 35,375 molecular weight. Mutant strains in which the cfxA structural gene was disrupted by insertional inactivation lost both Fxr and beta-lactamase activity.

Chloramphenicol

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Key Molecule: Chloramphenicol acetyltransferase (CAT) [4]

• Resistant Disease: Bacillus pumilus infection [ICD-11: 1C4Y.3]
• Molecule Alteration: Expression; Inherence
• Resistant Drug: Chloramphenicol
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Bacillus pumilus strain NCIB8600; 1408
• In Vitro Model: Bacillus subtilis strain BR151; 1423
• Experiment for Molecule Alteration: Restriction enzyme assay
• Mechanism Description: Genes (cat) specifying the enzyme CAT occur in a wide range of unrelated bacteria, where they confer resistance to the antibiotic Cm. Gene cat-86 of Bacillus pumilus, specifying chloramphenicol-inducible chloramphenicol acetyltransferase, was previously cloned in Bacillus subtilis on plasmid pUB110.

Chlortetracycline

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Tetracycline resistance protein TetQ (TETQ) [5]

• Resistant Disease: Bacteroides spp infection [ICD-11: 1C4Y.9]
• Molecule Alteration: Expression; Inherence
• Resistant Drug: Chlortetracycline
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli DH5alpha; 668369
• Experiment for Molecule Alteration: PCR; Dot blot and Southern blot analysis
• Experiment for Drug Resistance: MIC assay
• Mechanism Description: Tet36 is a new class of ribosome protection type tetracycline resistance protein and lead to drug resistance.

Clindamycin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: 23S ribosomal RNA methyltransferase Erm34 (ERM34) [6]

• Resistant Disease: Bacillus clausii infection [ICD-11: 1C4Y.1]
• Molecule Alteration: Methylation; Ribosomal methylation
• Resistant Drug: Clindamycin
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Bacillus clausii ATCC 21536; 79880
• Experiment for Molecule Alteration: Cloning experiments and gene seqencing assay
• Experiment for Drug Resistance: Agar dilution assay
• Mechanism Description: This pattern of resistance generally due to the presence of an erm gene encoding a ribosomal methylase.

Key Molecule: ErmR rRNA adenine N6-methyltransferase (ERMR) [2]

• Resistant Disease: Bacteroides fragilis infection [ICD-11: 1C4Y.6]
• Molecule Alteration: Expression; Inherence
• Resistant Drug: Clindamycin
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Bacteroides distasonis strains; 823
• In Vitro Model: Bacteroides distasonis strains V2002; 823
• In Vitro Model: Bacteroides distasonis strains V2003; 823
• In Vitro Model: Bacteroides distasonis strains V2004; 823
• In Vitro Model: Bacteroides fragilis strain; 817
• In Vitro Model: Bacteroides fragilis strain V503; 817
• In Vitro Model: Bacteroides ovatus strains; 28116
• In Vitro Model: Bacteroides ovatus strains V2008; 28116
• In Vitro Model: Bacteroides thetaiotaomicron strain; 818
• In Vitro Model: Bacteroides thetaiotaomicron strain V2005; 818
• In Vitro Model: Bacteroides thetaiotaomicron strain V2006; 818
• In Vitro Model: Bacteroides thetaiotaomicron strain V2007; 818
• In Vitro Model: Bacteroides uniformis strain; 820
• In Vitro Model: Bacteroides uniformis strain V1760; 820
• In Vitro Model: Bacteroides uniformis strain V1761; 820
• In Vitro Model: Bacteroides uniformis strain V1918; 820
• In Vitro Model: Bacteroides uniformis strain V1921; 820
• In Vitro Model: Bacteroides uniformis strain V2000; 820
• In Vitro Model: Bacteroides uniformis strain V2001; 820
• In Vitro Model: Bacteroides uniformis strain V528; 820
• In Vitro Model: Bacteroides uniformis strain V844; 820
• Experiment for Molecule Alteration: Southern blotting assay
• Mechanism Description: Clindamycin resistance in Bacteroides spp. is usually macrolide-lincosamide-streptogramin B (MLS) resistance conferred by erm genes which are similar to those seen in gram-positive, facultative anaerobes. Of 13 clinical isolates of the Bacteroides group, all were resistant to tetracycline (>10,ug/ml).

Key Molecule: ErmR rRNA adenine N6-methyltransferase (ERMR) [2]

• Resistant Disease: Bacteroides distasonis infection [ICD-11: 1C4Y.5]
• Molecule Alteration: Expression; Inherence
• Resistant Drug: Clindamycin
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Bacteroides distasonis strains; 823
• In Vitro Model: Bacteroides distasonis strains V2002; 823
• In Vitro Model: Bacteroides distasonis strains V2003; 823
• In Vitro Model: Bacteroides distasonis strains V2004; 823
• In Vitro Model: Bacteroides fragilis strain; 817
• In Vitro Model: Bacteroides fragilis strain V503; 817
• In Vitro Model: Bacteroides ovatus strains; 28116
• In Vitro Model: Bacteroides ovatus strains V2008; 28116
• In Vitro Model: Bacteroides thetaiotaomicron strain; 818
• In Vitro Model: Bacteroides thetaiotaomicron strain V2005; 818
• In Vitro Model: Bacteroides thetaiotaomicron strain V2006; 818
• In Vitro Model: Bacteroides thetaiotaomicron strain V2007; 818
• In Vitro Model: Bacteroides uniformis strain; 820
• In Vitro Model: Bacteroides uniformis strain V1760; 820
• In Vitro Model: Bacteroides uniformis strain V1761; 820
• In Vitro Model: Bacteroides uniformis strain V1918; 820
• In Vitro Model: Bacteroides uniformis strain V1921; 820
• In Vitro Model: Bacteroides uniformis strain V2000; 820
• In Vitro Model: Bacteroides uniformis strain V2001; 820
• In Vitro Model: Bacteroides uniformis strain V528; 820
• In Vitro Model: Bacteroides uniformis strain V844; 820
• Experiment for Molecule Alteration: Southern blotting assay
• Mechanism Description: Clindamycin resistance in Bacteroides spp. is usually macrolide-lincosamide-streptogramin B (MLS) resistance conferred by erm genes which are similar to those seen in gram-positive, facultative anaerobes. Of 13 clinical isolates of the Bacteroides group, all were resistant to tetracycline (>10,ug/ml).

Key Molecule: ErmR rRNA adenine N6-methyltransferase (ERMR) [2]

• Resistant Disease: Bacteroides thetaiotaomicron infection [ICD-11: 1C4Y.10]
• Molecule Alteration: Expression; Inherence
• Resistant Drug: Clindamycin
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Bacteroides distasonis strains; 823
• In Vitro Model: Bacteroides distasonis strains V2002; 823
• In Vitro Model: Bacteroides distasonis strains V2003; 823
• In Vitro Model: Bacteroides distasonis strains V2004; 823
• In Vitro Model: Bacteroides fragilis strain; 817
• In Vitro Model: Bacteroides fragilis strain V503; 817
• In Vitro Model: Bacteroides ovatus strains; 28116
• In Vitro Model: Bacteroides ovatus strains V2008; 28116
• In Vitro Model: Bacteroides thetaiotaomicron strain; 818
• In Vitro Model: Bacteroides thetaiotaomicron strain V2005; 818
• In Vitro Model: Bacteroides thetaiotaomicron strain V2006; 818
• In Vitro Model: Bacteroides thetaiotaomicron strain V2007; 818
• In Vitro Model: Bacteroides uniformis strain; 820
• In Vitro Model: Bacteroides uniformis strain V1760; 820
• In Vitro Model: Bacteroides uniformis strain V1761; 820
• In Vitro Model: Bacteroides uniformis strain V1918; 820
• In Vitro Model: Bacteroides uniformis strain V1921; 820
• In Vitro Model: Bacteroides uniformis strain V2000; 820
• In Vitro Model: Bacteroides uniformis strain V2001; 820
• In Vitro Model: Bacteroides uniformis strain V528; 820
• In Vitro Model: Bacteroides uniformis strain V844; 820
• Experiment for Molecule Alteration: Southern blotting assay
• Mechanism Description: Clindamycin resistance in Bacteroides spp. is usually macrolide-lincosamide-streptogramin B (MLS) resistance conferred by erm genes which are similar to those seen in gram-positive, facultative anaerobes. Of 13 clinical isolates of the Bacteroides group, all were resistant to tetracycline (>10,ug/ml).

Key Molecule: ErmR rRNA adenine N6-methyltransferase (ERMR) [2]

• Resistant Disease: Bacteroides ovatus infection [ICD-11: 1C4Y.8]
• Molecule Alteration: Expression; Inherence
• Resistant Drug: Clindamycin
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Bacteroides distasonis strains; 823
• In Vitro Model: Bacteroides distasonis strains V2002; 823
• In Vitro Model: Bacteroides distasonis strains V2003; 823
• In Vitro Model: Bacteroides distasonis strains V2004; 823
• In Vitro Model: Bacteroides fragilis strain; 817
• In Vitro Model: Bacteroides fragilis strain V503; 817
• In Vitro Model: Bacteroides ovatus strains; 28116
• In Vitro Model: Bacteroides ovatus strains V2008; 28116
• In Vitro Model: Bacteroides thetaiotaomicron strain; 818
• In Vitro Model: Bacteroides thetaiotaomicron strain V2005; 818
• In Vitro Model: Bacteroides thetaiotaomicron strain V2006; 818
• In Vitro Model: Bacteroides thetaiotaomicron strain V2007; 818
• In Vitro Model: Bacteroides uniformis strain; 820
• In Vitro Model: Bacteroides uniformis strain V1760; 820
• In Vitro Model: Bacteroides uniformis strain V1761; 820
• In Vitro Model: Bacteroides uniformis strain V1918; 820
• In Vitro Model: Bacteroides uniformis strain V1921; 820
• In Vitro Model: Bacteroides uniformis strain V2000; 820
• In Vitro Model: Bacteroides uniformis strain V2001; 820
• In Vitro Model: Bacteroides uniformis strain V528; 820
• In Vitro Model: Bacteroides uniformis strain V844; 820
• Experiment for Molecule Alteration: Southern blotting assay
• Mechanism Description: Clindamycin resistance in Bacteroides spp. is usually macrolide-lincosamide-streptogramin B (MLS) resistance conferred by erm genes which are similar to those seen in gram-positive, facultative anaerobes. Of 13 clinical isolates of the Bacteroides group, all were resistant to tetracycline (>10,ug/ml).

Demeclocycline

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Tetracycline resistance protein TetQ (TETQ) [5]

• Resistant Disease: Bacteroides spp infection [ICD-11: 1C4Y.9]
• Molecule Alteration: Expression; Inherence
• Resistant Drug: Demeclocycline
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli DH5alpha; 668369
• Experiment for Molecule Alteration: PCR; Dot blot and Southern blot analysis
• Experiment for Drug Resistance: MIC assay
• Mechanism Description: Tet36 is a new class of ribosome protection type tetracycline resistance protein and lead to drug resistance.

Doxycycline

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Tetracycline resistance protein TetQ (TETQ) [5]

• Resistant Disease: Bacteroides spp infection [ICD-11: 1C4Y.9]
• Molecule Alteration: Expression; Inherence
• Resistant Drug: Doxycycline
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli DH5alpha; 668369
• Experiment for Molecule Alteration: PCR; Dot blot and Southern blot analysis
• Experiment for Drug Resistance: MIC assay
• Mechanism Description: Tet36 is a new class of ribosome protection type tetracycline resistance protein and lead to drug resistance.

Erythromycin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: 23S ribosomal RNA methyltransferase Erm34 (ERM34) [6]

• Resistant Disease: Bacillus clausii infection [ICD-11: 1C4Y.1]
• Molecule Alteration: Methylation; Ribosomal methylation
• Resistant Drug: Erythromycin
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Bacillus clausii ATCC 21536; 79880
• Experiment for Molecule Alteration: Cloning experiments and gene seqencing assay
• Experiment for Drug Resistance: Agar dilution assay
• Mechanism Description: This pattern of resistance generally due to the presence of an erm gene encoding a ribosomal methylase.

Key Molecule: rRNA adenine N-6-methyltransferase ermG (ERMG) [7]

• Resistant Disease: Bacillus sphaericus infection [ICD-11: 1C4Y.4]
• Molecule Alteration: Expression; Inherence
• Resistant Drug: Erythromycin
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Bacillus subtilis strain BD1107; 1423
• In Vitro Model: Bacillus subtilis strain BD1117; 1423
• In Vitro Model: Bacillus subtilis strain BD1146; 1423
• In Vitro Model: Bacillus subtilis strain BD1156; 1423
• In Vitro Model: Bacillus subtilis strain BD1158; 1423
• In Vitro Model: Bacillus subtilis strain BD624; 1423
• In Vitro Model: Bacillus subtilis strain BD629; 1423
• In Vitro Model: Bacillus subtilis strain BD630; 1423
• In Vitro Model: Bacillus subtilis strain CU403; 1423
• Experiment for Molecule Alteration: Southern blotting assay
• Mechanism Description: One of the mechanisms of bacterial resistance to aminoglycosides is the production of aminoglycoside N-acetyl-transferase (AAC) enzymes which acetylate the amino groups present in the molecule of the aminoglycoside, preventing their interaction with the ribosome. ermG specifies a 29,000-dalton protein, the synthesis of which is induced by erythromycin. S1 nuclease mapping was used to identify the transcriptional start site. These experiments demonstrated the presence on the ermG mRNA of a 197 to 198-base leader.

Key Molecule: ErmR rRNA adenine N6-methyltransferase (ERMR) [2]

• Resistant Disease: Bacteroides fragilis infection [ICD-11: 1C4Y.6]
• Molecule Alteration: Expression; Inherence
• Resistant Drug: Erythromycin
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Bacteroides distasonis strains; 823
• In Vitro Model: Bacteroides distasonis strains V2002; 823
• In Vitro Model: Bacteroides distasonis strains V2003; 823
• In Vitro Model: Bacteroides distasonis strains V2004; 823
• In Vitro Model: Bacteroides fragilis strain; 817
• In Vitro Model: Bacteroides fragilis strain V503; 817
• In Vitro Model: Bacteroides ovatus strains; 28116
• In Vitro Model: Bacteroides ovatus strains V2008; 28116
• In Vitro Model: Bacteroides thetaiotaomicron strain; 818
• In Vitro Model: Bacteroides thetaiotaomicron strain V2005; 818
• In Vitro Model: Bacteroides thetaiotaomicron strain V2006; 818
• In Vitro Model: Bacteroides thetaiotaomicron strain V2007; 818
• In Vitro Model: Bacteroides uniformis strain; 820
• In Vitro Model: Bacteroides uniformis strain V1760; 820
• In Vitro Model: Bacteroides uniformis strain V1761; 820
• In Vitro Model: Bacteroides uniformis strain V1918; 820
• In Vitro Model: Bacteroides uniformis strain V1921; 820
• In Vitro Model: Bacteroides uniformis strain V2000; 820
• In Vitro Model: Bacteroides uniformis strain V2001; 820
• In Vitro Model: Bacteroides uniformis strain V528; 820
• In Vitro Model: Bacteroides uniformis strain V844; 820
• Experiment for Molecule Alteration: Southern blotting assay
• Mechanism Description: Clindamycin resistance in Bacteroides spp. is usually macrolide-lincosamide-streptogramin B (MLS) resistance conferred by erm genes which are similar to those seen in gram-positive, facultative anaerobes. Of 13 clinical isolates of the Bacteroides group, all were resistant to tetracycline (>10,ug/ml). Seven of the eight clindamycin-resistant clinical isolates constitutively expressed erythromycin resistance and had a high level of resistance to clindamycin (> 10ug/ml). V2002 was susceptible to erythromycin.

Key Molecule: ErmR rRNA adenine N6-methyltransferase (ERMR) [2]

• Resistant Disease: Bacteroides thetaiotaomicron infection [ICD-11: 1C4Y.10]
• Molecule Alteration: Expression; Inherence
• Resistant Drug: Erythromycin
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Bacteroides distasonis strains; 823
• In Vitro Model: Bacteroides distasonis strains V2002; 823
• In Vitro Model: Bacteroides distasonis strains V2003; 823
• In Vitro Model: Bacteroides distasonis strains V2004; 823
• In Vitro Model: Bacteroides fragilis strain; 817
• In Vitro Model: Bacteroides fragilis strain V503; 817
• In Vitro Model: Bacteroides ovatus strains; 28116
• In Vitro Model: Bacteroides ovatus strains V2008; 28116
• In Vitro Model: Bacteroides thetaiotaomicron strain; 818
• In Vitro Model: Bacteroides thetaiotaomicron strain V2005; 818
• In Vitro Model: Bacteroides thetaiotaomicron strain V2006; 818
• In Vitro Model: Bacteroides thetaiotaomicron strain V2007; 818
• In Vitro Model: Bacteroides uniformis strain; 820
• In Vitro Model: Bacteroides uniformis strain V1760; 820
• In Vitro Model: Bacteroides uniformis strain V1761; 820
• In Vitro Model: Bacteroides uniformis strain V1918; 820
• In Vitro Model: Bacteroides uniformis strain V1921; 820
• In Vitro Model: Bacteroides uniformis strain V2000; 820
• In Vitro Model: Bacteroides uniformis strain V2001; 820
• In Vitro Model: Bacteroides uniformis strain V528; 820
• In Vitro Model: Bacteroides uniformis strain V844; 820
• Experiment for Molecule Alteration: Southern blotting assay
• Mechanism Description: Clindamycin resistance in Bacteroides spp. is usually macrolide-lincosamide-streptogramin B (MLS) resistance conferred by erm genes which are similar to those seen in gram-positive, facultative anaerobes. Of 13 clinical isolates of the Bacteroides group, all were resistant to tetracycline (>10,ug/ml). Seven of the eight clindamycin-resistant clinical isolates constitutively expressed erythromycin resistance and had a high level of resistance to clindamycin (> 10ug/ml). V2002 was susceptible to erythromycin.

Key Molecule: ErmR rRNA adenine N6-methyltransferase (ERMR) [2]

• Resistant Disease: Bacteroides ovatus infection [ICD-11: 1C4Y.8]
• Molecule Alteration: Expression; Inherence
• Resistant Drug: Erythromycin
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Bacteroides distasonis strains; 823
• In Vitro Model: Bacteroides distasonis strains V2002; 823
• In Vitro Model: Bacteroides distasonis strains V2003; 823
• In Vitro Model: Bacteroides distasonis strains V2004; 823
• In Vitro Model: Bacteroides fragilis strain; 817
• In Vitro Model: Bacteroides fragilis strain V503; 817
• In Vitro Model: Bacteroides ovatus strains; 28116
• In Vitro Model: Bacteroides ovatus strains V2008; 28116
• In Vitro Model: Bacteroides thetaiotaomicron strain; 818
• In Vitro Model: Bacteroides thetaiotaomicron strain V2005; 818
• In Vitro Model: Bacteroides thetaiotaomicron strain V2006; 818
• In Vitro Model: Bacteroides thetaiotaomicron strain V2007; 818
• In Vitro Model: Bacteroides uniformis strain; 820
• In Vitro Model: Bacteroides uniformis strain V1760; 820
• In Vitro Model: Bacteroides uniformis strain V1761; 820
• In Vitro Model: Bacteroides uniformis strain V1918; 820
• In Vitro Model: Bacteroides uniformis strain V1921; 820
• In Vitro Model: Bacteroides uniformis strain V2000; 820
• In Vitro Model: Bacteroides uniformis strain V2001; 820
• In Vitro Model: Bacteroides uniformis strain V528; 820
• In Vitro Model: Bacteroides uniformis strain V844; 820
• Experiment for Molecule Alteration: Southern blotting assay
• Mechanism Description: Clindamycin resistance in Bacteroides spp. is usually macrolide-lincosamide-streptogramin B (MLS) resistance conferred by erm genes which are similar to those seen in gram-positive, facultative anaerobes. Of 13 clinical isolates of the Bacteroides group, all were resistant to tetracycline (>10,ug/ml). Seven of the eight clindamycin-resistant clinical isolates constitutively expressed erythromycin resistance and had a high level of resistance to clindamycin (> 10ug/ml). V2002 was susceptible to erythromycin.

Lincomycin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: 23S ribosomal RNA methyltransferase Erm34 (ERM34) [6]

• Resistant Disease: Bacillus clausii infection [ICD-11: 1C4Y.1]
• Molecule Alteration: Methylation; Ribosomal methylation
• Resistant Drug: Lincomycin
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Bacillus clausii ATCC 21536; 79880
• Experiment for Molecule Alteration: Cloning experiments and gene seqencing assay
• Experiment for Drug Resistance: Agar dilution assay
• Mechanism Description: This pattern of resistance generally due to the presence of an erm gene encoding a ribosomal methylase.

Macrolides

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: rRNA adenine N-6-methyltransferase ermG (ERMG) [7]

• Resistant Disease: Bacillus sphaericus infection [ICD-11: 1C4Y.4]
• Molecule Alteration: Expression; Inherence
• Resistant Drug: Macrolides
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Bacillus subtilis strain BD1107; 1423
• In Vitro Model: Bacillus subtilis strain BD1117; 1423
• In Vitro Model: Bacillus subtilis strain BD1146; 1423
• In Vitro Model: Bacillus subtilis strain BD1156; 1423
• In Vitro Model: Bacillus subtilis strain BD1158; 1423
• In Vitro Model: Bacillus subtilis strain BD624; 1423
• In Vitro Model: Bacillus subtilis strain BD629; 1423
• In Vitro Model: Bacillus subtilis strain BD630; 1423
• In Vitro Model: Bacillus subtilis strain CU403; 1423
• Experiment for Molecule Alteration: Southern blotting assay
• Mechanism Description: One of the mechanisms of bacterial resistance to aminoglycosides is the production of aminoglycoside N-acetyl-transferase (AAC) enzymes which acetylate the amino groups present in the molecule of the aminoglycoside, preventing their interaction with the ribosome. ermG specifies a 29,000-dalton protein, the synthesis of which is induced by erythromycin. S1 nuclease mapping was used to identify the transcriptional start site. These experiments demonstrated the presence on the ermG mRNA of a 197 to 198-base leader.

Metronidazole

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Key Molecule: Glycosyltransferase Bme (BME) [8]

• Resistant Disease: Bacillus clausii infection [ICD-11: 1C4Y.1]
• Molecule Alteration: Expression; Inherence
• Resistant Drug: Metronidazole
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Vero cells; Kidney; Chlorocebus sabaeus (Green monkey) (Cercopithecus sabaeus); CVCL_0059
• Mechanism Description: E. coli mutants lacking the ability to reduce nitrate and chlorate, presumably reducing the rate of metronidazole uptake, are also resistant. A reduced growth rate is also associated with metronidazole resistance in C. perfringens, C. difficile and B. fragilis. Bacteroides resistance-nodulation-division (RND) efflux pumps (bme) also reduce susceptibility to metronidazole.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: HTH-type transcriptional activator (RHAR) [8]

• Resistant Disease: Bacillus clausii infection [ICD-11: 1C4Y.1]
• Molecule Alteration: Expression; Inherence
• Resistant Drug: Metronidazole
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Vero/TMPRSS2 cells; Kidney; Chlorocebus sabaeus (Green monkey) (Cercopithecus sabaeus); CVCL_YQ48
• Mechanism Description: In B. thetaiotaomicron, the upregulation of rhamnose catabolism regulatory protein (RhaR) results in a similar rerouting and increased resistance to metronidazole.

Key Molecule: G2-specific protein kinase (NIMA) [8]

• Resistant Disease: Bacillus clausii infection [ICD-11: 1C4Y.1]
• Molecule Alteration: Expression; Inherence
• Resistant Drug: Metronidazole
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Vero cells; Kidney; Chlorocebus sabaeus (Green monkey) (Cercopithecus sabaeus); CVCL_0059
• Mechanism Description: In B. fragilis, nimA encodes a 5-nitroimidazole reductase reducing the metronidazole analogue dimetronidazole (1,2-dimethyl-5-nitroimidazole) to the amino derivative, preventing ring fission and associated toxicity. The role of nim genes in metronidazole resistance is controversial. It has been established that overexpression of a NimA homologue from B. fragilis induces a 3-fold increase in metronidazole resistance in E. coli.

Minocycline

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Tetracycline resistance protein TetQ (TETQ) [5]

• Resistant Disease: Bacteroides spp infection [ICD-11: 1C4Y.9]
• Molecule Alteration: Expression; Inherence
• Resistant Drug: Minocycline
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli DH5alpha; 668369
• Experiment for Molecule Alteration: PCR; Dot blot and Southern blot analysis
• Experiment for Drug Resistance: MIC assay
• Mechanism Description: Tet36 is a new class of ribosome protection type tetracycline resistance protein and lead to drug resistance.

Oxytetracycline

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Tetracycline resistance protein TetQ (TETQ) [5]

• Resistant Disease: Bacteroides spp infection [ICD-11: 1C4Y.9]
• Molecule Alteration: Expression; Inherence
• Resistant Drug: Oxytetracycline
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli DH5alpha; 668369
• Experiment for Molecule Alteration: PCR; Dot blot and Southern blot analysis
• Experiment for Drug Resistance: MIC assay
• Mechanism Description: Tet36 is a new class of ribosome protection type tetracycline resistance protein and lead to drug resistance.

Ribostamycin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Key Molecule: Aminoglycoside 3'-phosphotransferase (A3AP) [9]

• Resistant Disease: Infection by Bacillus circulans [ICD-11: 1C4Y.12]
• Molecule Alteration: Expression; Inherence
• Resistant Drug: Ribostamycin
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli HB101; 634468
• In Vitro Model: Escherichia coli strain JM103; 83333
• In Vitro Model: Bacillus circulans strain; 1397
• In Vitro Model: Streptomyces lividans strain 66; 1200984
• In Vitro Model: Streptomyces lividans strain M180; 1916
• Experiment for Molecule Alteration: DNA sequencing assay
• Experiment for Drug Resistance: Semi-quantitative phosphocellulose-paper binding assay method assay
• Mechanism Description: We have elucidated the full nucleotide sequence of the aminoglycoside phosphotransferase (APH) gene from Bacillus circulans, which produces the aminoglycoside antibiotic butirosin.

Spiramycin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: 23S ribosomal RNA methyltransferase Erm34 (ERM34) [6]

• Resistant Disease: Bacillus clausii infection [ICD-11: 1C4Y.1]
• Molecule Alteration: Methylation; Ribosomal methylation
• Resistant Drug: Spiramycin
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Bacillus clausii ATCC 21536; 79880
• Experiment for Molecule Alteration: Cloning experiments and gene seqencing assay
• Experiment for Drug Resistance: Agar dilution assay
• Mechanism Description: This pattern of resistance generally due to the presence of an erm gene encoding a ribosomal methylase.

Tetracycline

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Tetracycline resistance protein TetQ (TETQ) [5]

• Resistant Disease: Bacteroides spp infection [ICD-11: 1C4Y.9]
• Molecule Alteration: Expression; Inherence
• Resistant Drug: Tetracycline
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli DH5alpha; 668369
• Experiment for Molecule Alteration: PCR; Dot blot and Southern blot analysis
• Experiment for Drug Resistance: MIC assay
• Mechanism Description: Tet36 is a new class of ribosome protection type tetracycline resistance protein and lead to drug resistance.

Key Molecule: Tetracycline resistance protein TetQ (TETQ) [2]

• Resistant Disease: Bacteroides fragilis infection [ICD-11: 1C4Y.6]
• Molecule Alteration: Expression; Inherence
• Resistant Drug: Tetracycline
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Bacteroides distasonis strains; 823
• In Vitro Model: Bacteroides distasonis strains V2002; 823
• In Vitro Model: Bacteroides distasonis strains V2003; 823
• In Vitro Model: Bacteroides distasonis strains V2004; 823
• In Vitro Model: Bacteroides fragilis strain; 817
• In Vitro Model: Bacteroides fragilis strain V503; 817
• In Vitro Model: Bacteroides ovatus strains; 28116
• In Vitro Model: Bacteroides ovatus strains V2008; 28116
• In Vitro Model: Bacteroides thetaiotaomicron strain; 818
• In Vitro Model: Bacteroides thetaiotaomicron strain V2005; 818
• In Vitro Model: Bacteroides thetaiotaomicron strain V2006; 818
• In Vitro Model: Bacteroides thetaiotaomicron strain V2007; 818
• In Vitro Model: Bacteroides uniformis strain; 820
• In Vitro Model: Bacteroides uniformis strain V1760; 820
• In Vitro Model: Bacteroides uniformis strain V1761; 820
• In Vitro Model: Bacteroides uniformis strain V1918; 820
• In Vitro Model: Bacteroides uniformis strain V1921; 820
• In Vitro Model: Bacteroides uniformis strain V2000; 820
• In Vitro Model: Bacteroides uniformis strain V2001; 820
• In Vitro Model: Bacteroides uniformis strain V528; 820
• In Vitro Model: Bacteroides uniformis strain V844; 820
• Experiment for Molecule Alteration: Southern blotting assay
• Mechanism Description: Of 13 clinical isolates of the Bacteroides group, all were resistant to tetracycline (>10,ug/ml). The source of tetracycline resistance was investigated with the recently cloned tetQ gene, a ribosomal protection gene.

Key Molecule: Tetracycline resistance protein TetQ (TETQ) [2]

• Resistant Disease: Bacteroides uniformis infection [ICD-11: 1C4Y.11]
• Molecule Alteration: Expression; Inherence
• Resistant Drug: Tetracycline
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Bacteroides distasonis strains; 823
• In Vitro Model: Bacteroides distasonis strains V2002; 823
• In Vitro Model: Bacteroides distasonis strains V2003; 823
• In Vitro Model: Bacteroides distasonis strains V2004; 823
• In Vitro Model: Bacteroides fragilis strain; 817
• In Vitro Model: Bacteroides fragilis strain V503; 817
• In Vitro Model: Bacteroides ovatus strains; 28116
• In Vitro Model: Bacteroides ovatus strains V2008; 28116
• In Vitro Model: Bacteroides thetaiotaomicron strain; 818
• In Vitro Model: Bacteroides thetaiotaomicron strain V2005; 818
• In Vitro Model: Bacteroides thetaiotaomicron strain V2006; 818
• In Vitro Model: Bacteroides thetaiotaomicron strain V2007; 818
• In Vitro Model: Bacteroides uniformis strain; 820
• In Vitro Model: Bacteroides uniformis strain V1760; 820
• In Vitro Model: Bacteroides uniformis strain V1761; 820
• In Vitro Model: Bacteroides uniformis strain V1918; 820
• In Vitro Model: Bacteroides uniformis strain V1921; 820
• In Vitro Model: Bacteroides uniformis strain V2000; 820
• In Vitro Model: Bacteroides uniformis strain V2001; 820
• In Vitro Model: Bacteroides uniformis strain V528; 820
• In Vitro Model: Bacteroides uniformis strain V844; 820
• Experiment for Molecule Alteration: Southern blotting assay
• Mechanism Description: Of 13 clinical isolates of the Bacteroides group, all were resistant to tetracycline (>10,ug/ml). The source of tetracycline resistance was investigated with the recently cloned tetQ gene, a ribosomal protection gene.

Key Molecule: Tetracycline resistance protein TetQ (TETQ) [2]

• Resistant Disease: Bacteroides distasonis infection [ICD-11: 1C4Y.5]
• Molecule Alteration: Expression; Inherence
• Resistant Drug: Tetracycline
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Bacteroides distasonis strains; 823
• In Vitro Model: Bacteroides distasonis strains V2002; 823
• In Vitro Model: Bacteroides distasonis strains V2003; 823
• In Vitro Model: Bacteroides distasonis strains V2004; 823
• In Vitro Model: Bacteroides fragilis strain; 817
• In Vitro Model: Bacteroides fragilis strain V503; 817
• In Vitro Model: Bacteroides ovatus strains; 28116
• In Vitro Model: Bacteroides ovatus strains V2008; 28116
• In Vitro Model: Bacteroides thetaiotaomicron strain; 818
• In Vitro Model: Bacteroides thetaiotaomicron strain V2005; 818
• In Vitro Model: Bacteroides thetaiotaomicron strain V2006; 818
• In Vitro Model: Bacteroides thetaiotaomicron strain V2007; 818
• In Vitro Model: Bacteroides uniformis strain; 820
• In Vitro Model: Bacteroides uniformis strain V1760; 820
• In Vitro Model: Bacteroides uniformis strain V1761; 820
• In Vitro Model: Bacteroides uniformis strain V1918; 820
• In Vitro Model: Bacteroides uniformis strain V1921; 820
• In Vitro Model: Bacteroides uniformis strain V2000; 820
• In Vitro Model: Bacteroides uniformis strain V2001; 820
• In Vitro Model: Bacteroides uniformis strain V528; 820
• In Vitro Model: Bacteroides uniformis strain V844; 820
• Experiment for Molecule Alteration: Southern blotting assay
• Mechanism Description: Of 13 clinical isolates of the Bacteroides group, all were resistant to tetracycline (>10,ug/ml). The source of tetracycline resistance was investigated with the recently cloned tetQ gene, a ribosomal protection gene.

Key Molecule: Tetracycline resistance protein TetQ (TETQ) [2]

• Resistant Disease: Bacteroides thetaiotaomicron infection [ICD-11: 1C4Y.10]
• Molecule Alteration: Expression; Inherence
• Resistant Drug: Tetracycline
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Bacteroides distasonis strains; 823
• In Vitro Model: Bacteroides distasonis strains V2002; 823
• In Vitro Model: Bacteroides distasonis strains V2003; 823
• In Vitro Model: Bacteroides distasonis strains V2004; 823
• In Vitro Model: Bacteroides fragilis strain; 817
• In Vitro Model: Bacteroides fragilis strain V503; 817
• In Vitro Model: Bacteroides ovatus strains; 28116
• In Vitro Model: Bacteroides ovatus strains V2008; 28116
• In Vitro Model: Bacteroides thetaiotaomicron strain; 818
• In Vitro Model: Bacteroides thetaiotaomicron strain V2005; 818
• In Vitro Model: Bacteroides thetaiotaomicron strain V2006; 818
• In Vitro Model: Bacteroides thetaiotaomicron strain V2007; 818
• In Vitro Model: Bacteroides uniformis strain; 820
• In Vitro Model: Bacteroides uniformis strain V1760; 820
• In Vitro Model: Bacteroides uniformis strain V1761; 820
• In Vitro Model: Bacteroides uniformis strain V1918; 820
• In Vitro Model: Bacteroides uniformis strain V1921; 820
• In Vitro Model: Bacteroides uniformis strain V2000; 820
• In Vitro Model: Bacteroides uniformis strain V2001; 820
• In Vitro Model: Bacteroides uniformis strain V528; 820
• In Vitro Model: Bacteroides uniformis strain V844; 820
• Experiment for Molecule Alteration: Southern blotting assay
• Mechanism Description: Of 13 clinical isolates of the Bacteroides group, all were resistant to tetracycline (>10,ug/ml). The source of tetracycline resistance was investigated with the recently cloned tetQ gene, a ribosomal protection gene.

Key Molecule: Tetracycline resistance protein TetQ (TETQ) [2]

• Resistant Disease: Bacteroides ovatus infection [ICD-11: 1C4Y.8]
• Molecule Alteration: Expression; Inherence
• Resistant Drug: Tetracycline
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Bacteroides distasonis strains; 823
• In Vitro Model: Bacteroides distasonis strains V2002; 823
• In Vitro Model: Bacteroides distasonis strains V2003; 823
• In Vitro Model: Bacteroides distasonis strains V2004; 823
• In Vitro Model: Bacteroides fragilis strain; 817
• In Vitro Model: Bacteroides fragilis strain V503; 817
• In Vitro Model: Bacteroides ovatus strains; 28116
• In Vitro Model: Bacteroides ovatus strains V2008; 28116
• In Vitro Model: Bacteroides thetaiotaomicron strain; 818
• In Vitro Model: Bacteroides thetaiotaomicron strain V2005; 818
• In Vitro Model: Bacteroides thetaiotaomicron strain V2006; 818
• In Vitro Model: Bacteroides thetaiotaomicron strain V2007; 818
• In Vitro Model: Bacteroides uniformis strain; 820
• In Vitro Model: Bacteroides uniformis strain V1760; 820
• In Vitro Model: Bacteroides uniformis strain V1761; 820
• In Vitro Model: Bacteroides uniformis strain V1918; 820
• In Vitro Model: Bacteroides uniformis strain V1921; 820
• In Vitro Model: Bacteroides uniformis strain V2000; 820
• In Vitro Model: Bacteroides uniformis strain V2001; 820
• In Vitro Model: Bacteroides uniformis strain V528; 820
• In Vitro Model: Bacteroides uniformis strain V844; 820
• Experiment for Molecule Alteration: Southern blotting assay
• Mechanism Description: Of 13 clinical isolates of the Bacteroides group, all were resistant to tetracycline (>10,ug/ml). The source of tetracycline resistance was investigated with the recently cloned tetQ gene, a ribosomal protection gene.

Zithromax

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: 23S ribosomal RNA methyltransferase Erm34 (ERM34) [6]

• Resistant Disease: Bacillus clausii infection [ICD-11: 1C4Y.1]
• Molecule Alteration: Methylation; Ribosomal methylation
• Resistant Drug: Zithromax
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Bacillus clausii ATCC 21536; 79880
• Experiment for Molecule Alteration: Cloning experiments and gene seqencing assay
• Experiment for Drug Resistance: Agar dilution assay
• Mechanism Description: This pattern of resistance generally due to the presence of an erm gene encoding a ribosomal methylase.

Clinical Trial Drug(s) 2 drug(s) in total

Pristinamycin I

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: 23S ribosomal RNA methyltransferase Erm34 (ERM34) [6]

• Resistant Disease: Bacillus clausii infection [ICD-11: 1C4Y.1]
• Molecule Alteration: Methylation; Ribosomal methylation
• Resistant Drug: Pristinamycin I
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Bacillus clausii ATCC 21536; 79880
• Experiment for Molecule Alteration: Cloning experiments and gene seqencing assay
• Experiment for Drug Resistance: Agar dilution assay
• Mechanism Description: This pattern of resistance generally due to the presence of an erm gene encoding a ribosomal methylase.

Pristinamycin IA

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: 23S ribosomal RNA methyltransferase Erm34 (ERM34) [6]

• Resistant Disease: Bacillus clausii infection [ICD-11: 1C4Y.1]
• Molecule Alteration: Methylation; Ribosomal methylation
• Resistant Drug: Pristinamycin IA
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Bacillus clausii ATCC 21536; 79880
• Experiment for Molecule Alteration: Cloning experiments and gene seqencing assay
• Experiment for Drug Resistance: Agar dilution assay
• Mechanism Description: This pattern of resistance generally due to the presence of an erm gene encoding a ribosomal methylase.

Investigative Drug(s) 1 drug(s) in total

Butirosina

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Key Molecule: Aminoglycoside 3'-phosphotransferase (A3AP) [9]

• Resistant Disease: Infection by Bacillus circulans [ICD-11: 1C4Y.12]
• Molecule Alteration: Expression; Inherence
• Resistant Drug: Butirosina
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli HB101; 634468
• In Vitro Model: Escherichia coli strain JM103; 83333
• In Vitro Model: Bacillus circulans strain; 1397
• In Vitro Model: Streptomyces lividans strain 66; 1200984
• In Vitro Model: Streptomyces lividans strain M180; 1916
• Experiment for Molecule Alteration: DNA sequencing assay
• Experiment for Drug Resistance: Semi-quantitative phosphocellulose-paper binding assay method assay
• Mechanism Description: We have elucidated the full nucleotide sequence of the aminoglycoside phosphotransferase (APH) gene from Bacillus circulans, which produces the aminoglycoside antibiotic butirosin.

References

• Ref 1: Bacillus licheniformis bacitracin-resistance ABC transporter: relationship to mammalian multidrug resistance. Mol Microbiol. 1995 Jun;16(5):969-76. doi: 10.1111/j.1365-2958.1995.tb02322.x.
• Ref 2: Molecular survey of clindamycin and tetracycline resistance determinants in Bacteroides species. Antimicrob Agents Chemother. 1991 Nov;35(11):2415-8. doi: 10.1128/AAC.35.11.2415.
• Ref 3: Genetic and biochemical analysis of a novel Ambler class A beta-lactamase responsible for cefoxitin resistance in Bacteroides species. Antimicrob Agents Chemother. 1993 May;37(5):1028-36. doi: 10.1128/AAC.37.5.1028.
• Ref 4: Nucleotide sequence of a Bacillus pumilus gene specifying chloramphenicol acetyltransferase. Gene. 1983 Oct;24(2-3):163-9. doi: 10.1016/0378-1119(83)90076-8.
• Ref 5: Identification of a new ribosomal protection type of tetracycline resistance gene, tet(36), from swine manure pits. Appl Environ Microbiol. 2003 Jul;69(7):4151-8. doi: 10.1128/AEM.69.7.4151-4158.2003.
• Ref 6: Characterization of a new erm-related macrolide resistance gene present in probiotic strains of Bacillus clausii. Appl Environ Microbiol. 2004 Jan;70(1):280-4. doi: 10.1128/AEM.70.1.280-284.2004.
• Ref 7: Cloning and analysis of ermG, a new macrolide-lincosamide-streptogramin B resistance element from Bacillus sphaericus. J Bacteriol. 1987 Jan;169(1):340-50. doi: 10.1128/jb.169.1.340-350.1987.
• Ref 8: Metronidazole: an update on metabolism, structure-cytotoxicity and resistance mechanisms .J Antimicrob Chemother. 2018 Feb 1;73(2):265-279. doi: 10.1093/jac/dkx351. 10.1093/jac/dkx351
• Ref 9: Sequence and interspecies transfer of an aminoglycoside phosphotransferase gene (APH) of Bacillus circulans. Self-defence mechanism in antibiotic-producing organisms. Biochem J. 1986 Jan 15;233(2):383-93. doi: 10.1042/bj2330383.