ArticleAntimicrobial agents and chemotherapy2005
A novel MATE family efflux pump contributes to the reduced susceptibility of laboratory-derived Staphylococcus aureus mutants to tigecycline.
Article in Antimicrobial agents and chemotherapy, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 103 papers.
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103 citing papers in PubMed.
- Genomic Characterization and Virulence Determinants ofAntibiotics (Basel, Switzerland) · 2026Article
- Global in silico genomic epidemiology of tetracycline resistance in Staphylococcus aureus: one health dynamics and genotype-phenotype associations.Molecular genetics and genomics : MGG · 2026Article
- Molecular insights into efflux pump genes in ciprofloxacin- and methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis clinical isolates from Iraq.Scientific reports · 2026Article
- Phenotypic and genetic stepwise changes inAntimicrobial agents and chemotherapy · 2025Article
- Mechanisms ofInternational journal of molecular sciences · 2025Article
- The Role of Protonation in the PfMATE Transporter Protein Structural Transitions.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Revisiting typing systems for group BMicrobial genomics · 2024Article
- Mechanisms of tigecycline resistance in Gram-negative bacteria: A narrative review.Engineering microbiology · 2024Review
- A novel member of drug/metabolite transporter (DMT) family efflux pump, SA00565, contributes to tetracycline antibiotics resistance inMicrobiology spectrum · 2024Article
- Efflux pumps: gatekeepers of antibiotic resistance inMicrobial cell (Graz, Austria) · 2024Article
- Efflux pump inhibitory potential of indole derivatives as an arsenal againstMicrobiology spectrum · 2023Article
- Tigecycline Resistance-Associated Mutations in the MepA Efflux Pump in Staphylococcus aureus.Microbiology spectrum · 2023Article
- Identification and Characterization of a Novel Major Facilitator Superfamily Efflux Pump, SA09310, Mediating Tetracycline Resistance in Staphylococcus aureus.Antimicrobial agents and chemotherapy · 2023Article
- Efflux Pump (QacA, QacB, and QacC) and β-Lactamase Inhibitors? An Evaluation of 1,8-Naphthyridines againstMolecules (Basel, Switzerland) · 2023Article
- Genetic characterization of Staphylococcus aureus isolated from Norway rats in Boston, Massachusetts.Veterinary medicine and science · 2023Article
- Atopic dermatitis-derivedFrontiers in cellular and infection microbiology · 2023Article
- Antimicrobial profile of coagulase-negative staphylococcus isolates from categories of individuals at a neonatal intensive care unit of a tertiary hospital, Ghana.The Pan African medical journal · 2023Article
- The Relationship between Ciprofloxacin Resistance and Genotypic Changes inPathogens (Basel, Switzerland) · 2022Article
- Antimicrobial Susceptibility Testing for Enterococci.Journal of clinical microbiology · 2022Review
- Methicillin Resistant Staphylococci Isolated from Goats and Their Farm Environments in Saudi Arabia Genotypically Linked to Known Human Clinical Isolates: a Pilot Study.Microbiology spectrum · 2022Article
43 more citing papers are in PubMed but not listed here.
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7 authors.
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Abstract
Tigecycline, an expanded-broad-spectrum glycylcycline antibiotic is not affected by the classical tetracycline resistance determinants found in Staphylococcus aureus. The in vitro selection of mutants with reduced susceptibility to tigecycline was evaluated for two methicillin-resistant S. aureus strains by serial passage in increasing concentrations of tigecycline. Both strains showed a stepwise elevation in tigecycline MIC over a period of 16 days, resulting in an increase in tigecycline MIC of 16- and 32-fold for N315 and Mu3, respectively. Transcriptional profiling revealed that both mutants exhibited over 100-fold increased expression of a gene cluster, mepRAB (multidrug export protein), encoding a MarR-like transcriptional regulator (mepR), a novel MATE family efflux pump (mepA), and a hypothetical protein of unknown function (mepB). Sequencing of the mepR gene in the mutant strains identified changes that presumably inactivated the MepR protein, which suggested that MepR functions as a repressor of mepA. Overexpression of mepA in a wild-type background caused a decrease in susceptibility to tigecycline and other substrates for MATE-type efflux pumps, although it was not sufficient to confer high-level resistance to tigecycline. Complementation of the mepR defect by overexpressing a wild-type mepR gene reduced mepA transcription and lowered the tigecycline MIC in the mutants. Transcription of tet(M) also increased by over 40-fold in the Mu3 mutant. This was attributed to a deletion in the promoter region of the gene that removed a stem-loop responsible for transcriptional attenuation. However, overexpression of the tet(M) transcript in a tigecycline-susceptible strain was not enough to significantly increase the MIC of tigecycline. These results suggest that the overexpression of mepA but not tet(M) may contribute to decreased susceptibility of tigecycline in S. aureus.
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