Activation of the Type III Secretion System of Enteropathogenic Escherichia coli Leads to Remodeling of Its Membrane Composition and Function

Anish Zacharia, Ritesh Ranjan Pal, Naama Katsowich, Chanchal Thomas Mannully, Aida Ibrahim, Sivan Alfandary, Raphael Serruya, Amit K. Baidya, Sigal Ben-Yehuda, Ilan Rosenshine, Arieh Moussaieff*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

The cell envelope of Gram-negative bacteria is a complex structure, essential for bacterial survival and for resistance to many antibiotics. Channels that cross the bacterial envelope and the host cell membrane form secretion systems that are activated upon attachment to host, enabling bacteria to inject effector molecules into the host cell, required for bacterium-host interaction. The type III secretion system (T3SS) is critical for the virulence of several pathogenic bacteria, including enteropathogenic Escherichia coli (EPEC). EPEC T3SS activation is associated with repression of carbon storage regulator (CsrA), resulting in gene expression remodeling, which is known to affect EPEC central carbon metabolism and contributes to the adaptation to a cell-adherent lifestyle in a poorly understood manner. We reasoned that the changes in the bacterial envelope upon attachment to the host and the activation of a secretion system may involve a modification of the lipid composition of bacterial envelope. Accordingly, we performed a lipidomics analysis on mutant strains that simulate T3SS activation. We saw a shift in glycerophospholipid metabolism toward the formation of lysophospholipids, attributed to corresponding upregulation of the phospholipase gene pldA and the acyltransferase gene ygiH upon T3SS activation in EPEC. We also detected a shift from menaquinones and ubiquinones to undecaprenyl lipids, concomitant with abnormal synthesis of O antigen. The remodeling of lipid metabolism is mediated by CsrA and associated with increased bacterial cell size and zeta potential and a corresponding alteration in EPEC permeability to vancomycin, increasing the sensitivity of T3SS-activated strains and of adherent wild-type EPEC to the antibiotic.

Original languageAmerican English
JournalmSystems
Volume7
Issue number3
DOIs
StatePublished - 28 Jun 2022

Bibliographical note

Publisher Copyright:
© 2022 Zacharia et al.

Keywords

  • CesT
  • CsrA
  • cell envelope
  • enteropathogenic E. coli
  • isoprenoids
  • lipid metabolism
  • lipidomics
  • phospholipids
  • terpenoids
  • type III secretion system

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