PMID:20211899
| Citation |
Ruiz, C and Levy, SB (2010) Many chromosomal genes modulate MarA-mediated multidrug resistance in Escherichia coli. Antimicrob. Agents Chemother. 54:2125-34 |
|---|---|
| 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. |
| Links |
PubMed PMC2863627 Online version:10.1128/AAC.01420-09 |
| Keywords |
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 |
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