ArticleAntimicrobial agents and chemotherapy2009
Fmt bypass in Pseudomonas aeruginosa causes induction of MexXY efflux pump expression.
Article in Antimicrobial agents and chemotherapy, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 44 citations in OpenAlex.
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- Antibiotic influx and efflux in Pseudomonas aeruginosa: Regulation and therapeutic implications.Microbial biotechnology · 2024Review
- Drug resistance and physiological roles of RND multidrug efflux pumps inMicrobiology (Reading, England) · 2023Article
- Effects of the order of exposure to antimicrobials on the incidence of multidrug-resistant Pseudomonas aeruginosa.Scientific reports · 2023Article
- Targeting the Holy Triangle of Quorum Sensing, Biofilm Formation, and Antibiotic Resistance in Pathogenic Bacteria.Microorganisms · 2022Review
- New Sequence Type ST3449 in Multidrug-ResistantAntibiotics (Basel, Switzerland) · 2021Article
- The Efflux Pump MexXY/OprM Contributes to the Tolerance and Acquired Resistance of Pseudomonas aeruginosa to Colistin.Antimicrobial agents and chemotherapy · 2020Article
- Interaction of ArmZ with the DNA-binding domain of MexZ induces expression ofAntimicrobial agents and chemotherapy · 2019Article
- Defects in Efflux (Antimicrobial agents and chemotherapy · 2019Article
- Target (MexB)- and Efflux-Based Mechanisms Decreasing the Effectiveness of the Efflux Pump Inhibitor D13-9001 inAntimicrobial agents and chemotherapy · 2019Article
- Mutations in GeneAntimicrobial agents and chemotherapy · 2018Article
- Determinants of Antibacterial Spectrum and Resistance Potential of the Elongation Factor G Inhibitor Argyrin B in Key Gram-Negative Pathogens.Antimicrobial agents and chemotherapy · 2017Article
- Lack of formylated methionyl-tRNA has pleiotropic effects on Bacillus subtilis.Microbiology (Reading, England) · 2017Article
- Article
- Mutant Alleles of lptD Increase the Permeability of Pseudomonas aeruginosa and Define Determinants of Intrinsic Resistance to Antibiotics.Antimicrobial agents and chemotherapy · 2016Article
- Polymyxin Susceptibility in Pseudomonas aeruginosa Linked to the MexXY-OprM Multidrug Efflux System.Antimicrobial agents and chemotherapy · 2015Article
- The challenge of efflux-mediated antibiotic resistance in Gram-negative bacteria.Clinical microbiology reviews · 2015Review
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The intrinsic resistance of P. aeruginosa PAO1 to the peptide deformylase inhibitor (PDF-I) LBM415 was mediated by the MexAB-OprM and MexXY-OprM efflux pumps, the latter of which was strongly induced by LBM415. Single-step exposure of PAO1 deleted for mexAB-oprM (therefore lacking both MexAB-OprM and MexXY-OprM functions) to PDF-Is selected for nfxB mutants, which express the MexCD-OprJ efflux pump, indicating that these compounds are also substrates for this pump. Selection of resistant mutants by use of levels of LBM415 greater than that accommodated by efflux yielded two additional groups of mutations, in the methionyl-tRNA(fmet) formyltransferase (fmt) and folD genes. Both mechanisms are known to impose an in vitro growth deficit (also observed here), presumably due to impairment of protein synthesis. We surmised that this inherent impairment of protein synthesis would upregulate expression of mexXY in a fashion similar to upregulation by LBM415 or by ribosome inhibitory compounds. Transcriptional profiling and/or mexX::lux promoter fusion analysis revealed that fmt and folD mutants were strongly upregulated for mexXY and another gene known to be required for upregulation of the pump, PA5471. Complementation of the fmt mutation in trans reversed this constitutive expression. This supports the notion that MexXY has a natural physiological function responding to impairment of ribosome function or protein synthesis and that fmt mutation (Fmt bypass) and folD mutation generate the intracellular mexXY-inducing signal.
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