Role of the multidrug resistance regulator MarA in global regulation of the hdeAB acid resistance operon in Escherichia coli.
MarA, a transcriptional regulator in Escherichia coli, affects functions such as multiple-antibiotic resistance (Mar) and virulence. Usually an activator, MarA is a repressor of hdeAB and other acid resistance genes. We found that, in wild-type cells grown in LB medium at pH 7.0 or pH 5.5, repression of hdeAB by MarA occurred only in stationary phase and was reduced in the absence of H-NS and GadE, the main regulators of hdeAB. Moreover, repression of hdeAB by MarA was greater in the absence of GadX or Lrp in exponential phase at pH 7.0 and in the absence of GadW or RpoS in stationary phase at pH 5.5. In turn, MarA enhanced repression of hdeAB by H-NS and hindered activation by GadE in stationary phase and also reduced the activity of GadX, GadW, RpoS, and Lrp on hdeAB under some conditions. As a result of its direct and indirect effects, overexpression of MarA prevented most of the induction of hdeAB expression as cells entered stationary phase and made the cells sevenfold more sensitive to acid challenge at pH 2.5. These findings show that repression of hdeAB by MarA depends on pH, growth phase, and other regulators of hdeAB and is associated with reduced resistance to acid conditions.
Ruiz
Cristian
C
Center for Adaptation Genetics and Drug Resistance, Tufts University School of Medicine, 136 Harrison Ave., Boston, MA 02111, USA.
McMurry
Laura M
LM
Levy
Stuart B
SB
D000143:Acids / Q000494:pharmacology; D051777:AraC Transcription Factor / Q000235:genetics / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D001483:Base Sequence; D001665:Binding Sites; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D024881:Drug Resistance, Bacterial / Q000235:genetics; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D006863:Hydrogen-Ion Concentration; D051756:Leucine-Responsive Regulatory Protein / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D009876:Operon / Q000235:genetics*; D011485:Protein Binding; D012808:Sigma Factor / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D000143:Acids; D051777:AraC Transcription Factor; D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; D029968:Escherichia coli Proteins; C479562:GadE protein, E coli; C474648:GadW protein, E coli; C446316:GadX protein, E coli; C031908:H-NS protein, bacteria; C497278:Lrp protein, E coli; C080002:MarA protein, E coli; D012808:Sigma Factor; D014157:Transcription Factors; C084501:hdeA protein, E coli; C084502:hdeB protein, E coli; C069567:sigma factor KatF protein, Bacteria; D051756:Leucine-Responsive Regulatory Protein