Molecule Information

General Information of the Molecule (ID: Mol04396)

• Name: Transmembrane protein 94 (TMEM94) ,Homo sapiens
• Synonyms: Endoplasmic reticulum magnesium ATPase
• Molecule Type: Protein
• Gene Name: TMEM94
• Gene ID: 9772
• Sequence:
  MDLKEKHLGEPPSALGLSTRKALSVLKEQLEAVLEGHLRERKKCLTWKEVWRSSFLHHSN
  RCSCFHWPGASLMLLAVLLLLGCCGGQPAGSRGVGLVNASALFLLLLLNLVLIGRQDRL
  K RREVERRLRGIIDQIQDALRDGREIQWPSAMYPDLHMPFAPSWSLHWAYRDGHLVNLP
  VS LLVEGDIIALRPGQESFASLRGIKDDEHIVLEPGDLFPPFSPPPSPRGEVERGPQSP
  QQH RLFRVLETPVIDNIRWCLDMALSRPVTALDNERFTVQSVMLHYAVPVVLAGFLITN
  ALRF IFSAPGVTSWQYTLLQLQVNGVLPILPLLFPVLWVLATACGEARVLAQMSKASPS
  SLLAK FSEDTLSSYTEAVSSQEMLRCIWGHFLRVLGGTSPTLSHSSSLLHSLGSVTVLC
  CVDKQG ILSWPNPSPETVLFFSGKVEPPHSSHEDLTDGLSTRSFCHPEPHERDALLAGS
  LNNTLHL SNEQERGDWPGEAPKPPEPYSHHKAHGRSKHPSGSNVSFSRDTEGGEEEPSK
  TQPGMESD PYEAEDFVCDYHLEMLSLSQDQQNPSCIQFDDSNWQLHLTSLKPLGLNVLL
  NLCDASVTE RLCRFSDHLCNIALQESHSAVLPVHVPWGLCELARLIGFTPGAKELFKQE
  NHLALYRLPS AETMKETSLGRLSCVTKRRPPLSHMISLFIKDTTTSTEQMLSHGTADVV
  LEACTDFWDGA DIYPLSGSDRKKVLDFYQRACLSGYCSAFAYKPMNCALSSQLNGKCIE
  LVQVPGQSSIFT MCELPSTIPIKQNARRSSWSSDEGIGEVLEKEDCMQALSGQIFMGMV
  SSQYQARLDIVRL IDGLVNACIRFVYFSLEDELKSKVFAEKMGLETGWNCHISLTPNGD
  MPGSEIPPSSPSHA GSLHDDLNQVSRDDAEGLLLMEEEGHSDLISFQPTDSDIPSFLED
  SNRAKLPRGIHQVRP HLQNIDNVPLLVPLFTDCTPETMCEMIKIMQEYGEVTCCLGSSA
  NLRNSCLFLQSDISIA LDPLYPSRCSWETFGYATSISMAQASDGLSPLQLSGQLNSLPC
  SLTFRQEETISIIRLIE QARHATYGIRKCFLFLLQCQLTLVVIQFLSCLVQLPPLLSTT
  DILWLSCFCYPLLSISLL GKPPHSSIMSMATGKNLQSIPKKTQHYFLLCFLLKFSLTIS
  SCLICFGFTLQSFCDSSRD RNLTNCSSVMLPSNDDRAPAWFEDFANGLLSAQKLTAALI
  VLHTVFISITHVHRTKPLWR KSPLTNLWWAVTVPVVLLGQVVQTAVDLQLWTHRDSHVH
  FGLEDVPLLTWLLGCLSLVLV VVTNEIVKLHEIRVRVRYQKRQKLQFETKLGMNSPF
• Function: Could function in the uptake of Mg from the cytosol intothe endoplasmic reticulum and regulate intracellular Mghomeostasis. {ECO:0000269|PubMed:38513662}.
• Uniprot ID: TMM94_HUMAN
• Ensembl ID: ENSG0000017772817
• HGNC ID: HGNC:28983

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens

Type(s) of Resistant Mechanism of This Molecule

  ADTT: Aberration of the Drug's Therapeutic Target

Drug Resistance Data Categorized by Drug

Approved Drug(s) 5 drug(s) in total

Doxorubicin

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Staphylococcus aureus infection [ICD-11: 1B54.0] [1]

• Sensitive Disease: Staphylococcus aureus infection [ICD-11: 1B54.0]
• Sensitive Drug: Doxorubicin
• Molecule Alteration: Methylation; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: S. aureus isolates; 41687
• Experiment for Molecule Alteration: PCR; Docking assay
• Experiment for Drug Resistance: Antimicrobial susceptibility testing; Phenotypic assay; MIC assay; Checkerboard microdilution assay
• Mechanism Description: This study aimed to identify the prevalence of erythromycin and erythromycin-induced resistance and assess for potential inhibitors. A total of 99 isolates were purified from various clinical sources. Phenotypic detection of macrolide-lincosamide-streptogramin B (MLSB)-resistance phenotypes was performed by D-test. MLSB-resistance genes were identified using PCR. Different compounds were tested for their effects on erythromycin and inducible clindamycin resistance by broth microdilution and checkerboard microdilution methods. The obtained data were evaluated using docking analysis. Ninety-one isolates were S. aureus. The prevalence of constitutive MLSB, inducible MLSB, and macrolide-streptogramin (MS) phenotypes was 39.6%, 14.3%, and 2.2%, respectively. Genes including ermC, ermA, ermB, msrA, msrB, lnuA, and mphC were found in 82.6%, 5.8%, 7.7%, 3.8%, 3.8%, 13.5%, and 3.8% of isolates, respectively. Erythromycin resistance was significantly reduced by doxorubicin, neomycin, and omeprazole. Quinine, ketoprofen, and fosfomycin combated and reversed erythromycin/clindamycin-induced resistance. This study highlighted the significance of managing antibiotic resistance and overcoming clindamycin treatment failure. Doxorubicin, neomycin, omeprazole, quinine, ketoprofen, and fosfomycin could be potential inhibitors of erythromycin and inducible clindamycin resistance.

Fosfomycin

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Staphylococcus aureus infection [ICD-11: 1B54.0] [1]

• Sensitive Disease: Staphylococcus aureus infection [ICD-11: 1B54.0]
• Sensitive Drug: Fosfomycin
• Molecule Alteration: Methylation; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: S. aureus isolates; 41687
• Experiment for Molecule Alteration: PCR; Docking assay
• Experiment for Drug Resistance: Antimicrobial susceptibility testing; Phenotypic assay; MIC assay; Checkerboard microdilution assay
• Mechanism Description: This study aimed to identify the prevalence of erythromycin and erythromycin-induced resistance and assess for potential inhibitors. A total of 99 isolates were purified from various clinical sources. Phenotypic detection of macrolide-lincosamide-streptogramin B (MLSB)-resistance phenotypes was performed by D-test. MLSB-resistance genes were identified using PCR. Different compounds were tested for their effects on erythromycin and inducible clindamycin resistance by broth microdilution and checkerboard microdilution methods. The obtained data were evaluated using docking analysis. Ninety-one isolates were S. aureus. The prevalence of constitutive MLSB, inducible MLSB, and macrolide-streptogramin (MS) phenotypes was 39.6%, 14.3%, and 2.2%, respectively. Genes including ermC, ermA, ermB, msrA, msrB, lnuA, and mphC were found in 82.6%, 5.8%, 7.7%, 3.8%, 3.8%, 13.5%, and 3.8% of isolates, respectively. Erythromycin resistance was significantly reduced by doxorubicin, neomycin, and omeprazole. Quinine, ketoprofen, and fosfomycin combated and reversed erythromycin/clindamycin-induced resistance. This study highlighted the significance of managing antibiotic resistance and overcoming clindamycin treatment failure. Doxorubicin, neomycin, omeprazole, quinine, ketoprofen, and fosfomycin could be potential inhibitors of erythromycin and inducible clindamycin resistance.

Framycetin

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Staphylococcus aureus infection [ICD-11: 1B54.0] [1]

• Sensitive Disease: Staphylococcus aureus infection [ICD-11: 1B54.0]
• Sensitive Drug: Framycetin
• Molecule Alteration: Methylation; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: S. aureus isolates; 41687
• Experiment for Molecule Alteration: PCR; Docking assay
• Experiment for Drug Resistance: Antimicrobial susceptibility testing; Phenotypic assay; MIC assay; Checkerboard microdilution assay
• Mechanism Description: This study aimed to identify the prevalence of erythromycin and erythromycin-induced resistance and assess for potential inhibitors. A total of 99 isolates were purified from various clinical sources. Phenotypic detection of macrolide-lincosamide-streptogramin B (MLSB)-resistance phenotypes was performed by D-test. MLSB-resistance genes were identified using PCR. Different compounds were tested for their effects on erythromycin and inducible clindamycin resistance by broth microdilution and checkerboard microdilution methods. The obtained data were evaluated using docking analysis. Ninety-one isolates were S. aureus. The prevalence of constitutive MLSB, inducible MLSB, and macrolide-streptogramin (MS) phenotypes was 39.6%, 14.3%, and 2.2%, respectively. Genes including ermC, ermA, ermB, msrA, msrB, lnuA, and mphC were found in 82.6%, 5.8%, 7.7%, 3.8%, 3.8%, 13.5%, and 3.8% of isolates, respectively. Erythromycin resistance was significantly reduced by doxorubicin, neomycin, and omeprazole. Quinine, ketoprofen, and fosfomycin combated and reversed erythromycin/clindamycin-induced resistance. This study highlighted the significance of managing antibiotic resistance and overcoming clindamycin treatment failure. Doxorubicin, neomycin, omeprazole, quinine, ketoprofen, and fosfomycin could be potential inhibitors of erythromycin and inducible clindamycin resistance.

Ketoprofen

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Staphylococcus aureus infection [ICD-11: 1B54.0] [1]

• Sensitive Disease: Staphylococcus aureus infection [ICD-11: 1B54.0]
• Sensitive Drug: Ketoprofen
• Molecule Alteration: Methylation; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: S. aureus isolates; 41687
• Experiment for Molecule Alteration: PCR; Docking assay
• Experiment for Drug Resistance: Antimicrobial susceptibility testing; Phenotypic assay; MIC assay; Checkerboard microdilution assay
• Mechanism Description: This study aimed to identify the prevalence of erythromycin and erythromycin-induced resistance and assess for potential inhibitors. A total of 99 isolates were purified from various clinical sources. Phenotypic detection of macrolide-lincosamide-streptogramin B (MLSB)-resistance phenotypes was performed by D-test. MLSB-resistance genes were identified using PCR. Different compounds were tested for their effects on erythromycin and inducible clindamycin resistance by broth microdilution and checkerboard microdilution methods. The obtained data were evaluated using docking analysis. Ninety-one isolates were S. aureus. The prevalence of constitutive MLSB, inducible MLSB, and macrolide-streptogramin (MS) phenotypes was 39.6%, 14.3%, and 2.2%, respectively. Genes including ermC, ermA, ermB, msrA, msrB, lnuA, and mphC were found in 82.6%, 5.8%, 7.7%, 3.8%, 3.8%, 13.5%, and 3.8% of isolates, respectively. Erythromycin resistance was significantly reduced by doxorubicin, neomycin, and omeprazole. Quinine, ketoprofen, and fosfomycin combated and reversed erythromycin/clindamycin-induced resistance. This study highlighted the significance of managing antibiotic resistance and overcoming clindamycin treatment failure. Doxorubicin, neomycin, omeprazole, quinine, ketoprofen, and fosfomycin could be potential inhibitors of erythromycin and inducible clindamycin resistance.

Quinine

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Staphylococcus aureus infection [ICD-11: 1B54.0] [1]

• Sensitive Disease: Staphylococcus aureus infection [ICD-11: 1B54.0]
• Sensitive Drug: Quinine
• Molecule Alteration: Methylation; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: S. aureus isolates; 41687
• Experiment for Molecule Alteration: PCR; Docking assay
• Experiment for Drug Resistance: Antimicrobial susceptibility testing; Phenotypic assay; MIC assay; Checkerboard microdilution assay
• Mechanism Description: This study aimed to identify the prevalence of erythromycin and erythromycin-induced resistance and assess for potential inhibitors. A total of 99 isolates were purified from various clinical sources. Phenotypic detection of macrolide-lincosamide-streptogramin B (MLSB)-resistance phenotypes was performed by D-test. MLSB-resistance genes were identified using PCR. Different compounds were tested for their effects on erythromycin and inducible clindamycin resistance by broth microdilution and checkerboard microdilution methods. The obtained data were evaluated using docking analysis. Ninety-one isolates were S. aureus. The prevalence of constitutive MLSB, inducible MLSB, and macrolide-streptogramin (MS) phenotypes was 39.6%, 14.3%, and 2.2%, respectively. Genes including ermC, ermA, ermB, msrA, msrB, lnuA, and mphC were found in 82.6%, 5.8%, 7.7%, 3.8%, 3.8%, 13.5%, and 3.8% of isolates, respectively. Erythromycin resistance was significantly reduced by doxorubicin, neomycin, and omeprazole. Quinine, ketoprofen, and fosfomycin combated and reversed erythromycin/clindamycin-induced resistance. This study highlighted the significance of managing antibiotic resistance and overcoming clindamycin treatment failure. Doxorubicin, neomycin, omeprazole, quinine, ketoprofen, and fosfomycin could be potential inhibitors of erythromycin and inducible clindamycin resistance.

References

• Ref 1: Inhibition of Erythromycin and Erythromycin-Induced Resistance among Staphylococcus aureus Clinical Isolates. Antibiotics (Basel). 2023 Mar 2;12(3):503.