論文 - 詳細
| RRC ID | 35281 |
|---|---|
| 著者 | Ruiz C, Levy SB. |
| タイトル | Many chromosomal genes modulate MarA-mediated multidrug resistance in Escherichia coli. |
| ジャーナル | Antimicrob Agents Chemother |
| Abstract |
Multidrug resistance (MDR) in clinical isolates of Escherichia coli can be associated with overexpression of marA, a transcription factor that upregulates multidrug efflux and downregulates membrane permeability. Using random transposome mutagenesis, we found that many chromosomal genes and environmental stimuli affected MarA-mediated antibiotic resistance. Seven genes affected resistance mediated by MarA in an antibiotic-specific way; these were mostly genes encoding unrelated enzymes, transporters, and unknown proteins. Other genes affected MarA-mediated resistance to all antibiotics tested. These genes were acrA, acrB, and tolC (which encode the major MarA-regulated multidrug efflux pump AcrAB-TolC), crp, cyaA, hns, and pcnB (four genes involved in global regulation of gene expression), and the unknown gene damX. The last five genes affected MarA-mediated MDR by altering marA expression or MarA function specifically on acrA. These findings demonstrate that MarA-mediated MDR is regulated at multiple levels by different genes and stimuli, which makes it both complex and fine-tuned and interconnects it with global cell regulation and metabolism. Such a regulation could contribute to the adaptation and spread of MDR strains and may be targeted to treat antibiotic-resistant E. coli and related pathogens. |
| 巻・号 | 54(5) |
| ページ | 2125-34 |
| 公開日 | 2010-5-1 |
| DOI | 10.1128/AAC.01420-09 |
| PII | AAC.01420-09 |
| PMID | 20211899 |
| PMC | PMC2863627 |
| MeSH | Anti-Bacterial Agents / pharmacology* Bacterial Outer Membrane Proteins / genetics Bacterial Outer Membrane Proteins / metabolism Chromosomes, Bacterial / genetics Colicins / genetics Colicins / metabolism Cyclic AMP Receptor Protein / genetics Cyclic AMP Receptor Protein / metabolism DNA-Binding Proteins / genetics* DNA-Binding Proteins / metabolism Drug Resistance, Bacterial / genetics* Drug Resistance, Multiple / genetics* Escherichia coli / drug effects* Escherichia coli / genetics* Escherichia coli / growth & development Escherichia coli Proteins / genetics* Escherichia coli Proteins / metabolism Fimbriae Proteins / genetics Fimbriae Proteins / metabolism Gene Expression Regulation, Bacterial / physiology Lipoproteins / genetics Lipoproteins / metabolism Membrane Transport Proteins / genetics Membrane Transport Proteins / metabolism Multidrug Resistance-Associated Proteins / genetics Multidrug Resistance-Associated Proteins / metabolism Mutagenesis Polynucleotide Adenylyltransferase / genetics Polynucleotide Adenylyltransferase / metabolism |
| IF | 4.904 |
| 引用数 | 32 |
| WOS 分野 | PHARMACOLOGY & PHARMACY MICROBIOLOGY |
| リソース情報 | |
| 原核生物(大腸菌) | ME9062(BW25113) JW5248-KC pNTR-SD |