1887

Abstract

Cationic antimicrobial peptides (CAMPs), a component of the mammalian immune system, protect the host from bacterial infections. The roles of the transcriptional regulators MarA, SoxS and Rob in susceptibility to these peptides were examined. Overexpression of , either in an antibiotic-resistant mutant or from a plasmid, decreased bacterial susceptibility to CAMPs. Overexpression of the 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 had little effect on CAMP susceptibility. The operon was upregulated when was incubated in sublethal amounts of CAMPs polymyxin B, LL-37 or human -defensin-1; however, this upregulation required Rob. Deletion of increased bacterial susceptibility to polymyxin B, LL-37 and human -defensin-1 peptides. Deletion of yielded an even greater increase in susceptibility to these peptides and also led to increased susceptibility to human -defensin-2. Inhibition of cellular proton-motive force increased peptide susceptibility for wild-type and deletion strains; however, it decreased susceptibility of mutants. These findings demonstrate that CAMPs are both inducers of -mediated drug resistance through interaction with Rob and also substrates for efflux in . The three related transcriptional regulators show different effects on bacterial cell susceptibility to CAMPs.

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2010-02-01
2020-08-03
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