Different effects of transcriptional regulators MarA, SoxS and Rob on susceptibility of Escherichia coli to cationic antimicrobial peptides (CAMPs): Rob-dependent CAMP induction of the marRAB operon.
Cationic antimicrobial peptides (CAMPs), a component of the mammalian immune system, protect the host from bacterial infections. The roles of the Escherichia coli transcriptional regulators MarA, SoxS and Rob in susceptibility to these peptides were examined. Overexpression of marA, either in an antibiotic-resistant marR mutant or from a plasmid, decreased bacterial susceptibility to CAMPs. Overexpression of the soxS gene from a plasmid, which decreased susceptibility to antibiotics, unexpectedly caused no decrease in CAMP susceptibility; instead it produced increased susceptibility to different CAMPs. Deletion or overexpression of rob had little effect on CAMP susceptibility. The marRAB operon was upregulated when E. coli was incubated in sublethal amounts of CAMPs polymyxin B, LL-37 or human beta-defensin-1; however, this upregulation required Rob. Deletion of acrAB increased bacterial susceptibility to polymyxin B, LL-37 and human beta-defensin-1 peptides. Deletion of tolC yielded an even greater increase in susceptibility to these peptides and also led to increased susceptibility to human alpha-defensin-2. Inhibition of cellular proton-motive force increased peptide susceptibility for wild-type and acrAB deletion strains; however, it decreased susceptibility of tolC mutants. These findings demonstrate that CAMPs are both inducers of marA-mediated drug resistance through interaction with Rob and also substrates for efflux in E. coli. The three related transcriptional regulators show different effects on bacterial cell susceptibility to CAMPs.
Warner
Douglas M
DM
Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, MA 02111, USA.|Center for Adaptation Genetics and Drug Resistance, Tufts University School of Medicine, Boston, MA 02111, USA.
Levy
Stuart B
SB
Department of Medicine, Tufts University School of Medicine, Boston, MA 02111, USA.|Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, MA 02111, USA.|Center for Adaptation Genetics and Drug Resistance, Tufts University School of Medicine, Boston, MA 02111, USA.
D000595:Amino Acid Sequence; D023181:Antimicrobial Cationic Peptides / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects / Q000235:genetics; D004926:Escherichia coli / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D005798:Genes, Bacterial; D006801:Humans; D026901:Membrane Transport Proteins / Q000378:metabolism; D009876:Operon; D011112:Polymyxin B / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology*; D054804:Cathelicidins
D023181:Antimicrobial Cationic Peptides; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; D029968:Escherichia coli Proteins; C080002:MarA protein, E coli; C080004:MarR protein, E coli; D026901:Membrane Transport Proteins; D012097:Repressor Proteins; C080267:Rob protein, E coli; D015534:Trans-Activators; C080003:multiple antibiotic resistance protein B; C073126:tolC protein, E coli; C070725:SoxS protein, E coli; D011112:Polymyxin B; D054804:Cathelicidins