Importance of the RpoE Regulon in Maintaining the Lipid Bilayer during Antimicrobial Treatment with the Polycationic Agent, Chlorhexidine

Sinisa Vidovic, Prabhakara Medihala, James J. Dynes, Prasad Daida, Vladimir Vujanovic, Adam P. Hitchcock, Deeksha Shetty, Haixia Zhang, David R. Brown, John R. Lawrence, Darren R. Korber

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

The emergence of multidrug resistance in bacteria has reached alarming levels. To solve this growing problem, discovery of novel cellular targets or pathways important for antimicrobial resistance is urgently needed. In this study, we explored how the alternative sigma factor, RpoE, protects Escherichia coli O157 against the toxic effects of the polycationic antimicrobial agent, chlorhexidine (CHX). Susceptibility of this organism to CHX was found to directly correlate to the growth rate, with the faster replicating wild-type being more susceptible to CHX than its more slowly replicating ΔrpoE O157 mutant. Once the wild-type and rpoE mutant strains had undergone growth arrest (entered the stationary growth phase), their resistance to CHX became entirely dependent on the functionality of RpoE. The RpoE regulon plays a critical role in maintaining the integrity of the asymmetric lipid bilayer of E. coli, thereby preventing the intracellular accumulation of CHX. Finally, using a single-cell, high-resolution, synchrotron-based approach, we discovered a subpopulation of the rpoE mutant strain with no detectable intracellular CHX, a predominant characteristic of the wild-type CHX-resistant population. This finding reveals a role of phenotypic heterogeneity in antimicrobial resistance.

Original languageEnglish (US)
Article number1700285
JournalProteomics
Volume18
Issue number3-4
DOIs
StatePublished - Feb 1 2018

Keywords

  • antimicrobial resistance
  • extracytoplasmic stress response
  • outer membrane proteins
  • rpoE sigma factor

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