Shigella flexneri Adapts to Niche-Specific Stresses through Modifications in Cell Envelope Composition and Decoration

Alice Ascari, Jack K. Waters, Renato Morona, Bart A. Eijkelkamp

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Shigella flexneri is the primary causative agent of worldwide shigellosis. As the pathogen transverses the distinct niches of the gastrointestinal tract it necessitates dynamic adaptation strategies to mitigate host antimicrobials such as dietary fatty acids (FAs) and the bile salt, deoxycholate (DOC). This study investigates the dynamics of the S. flexneri cell envelope, by interrogating adaptations following FA or DOC exposure. We deciphered the effects of FAs and DOC on bacterial membrane fatty acid and lipopolysaccharide (LPS) compositions. We identified novel LPS-based strategies by the pathogen to support resistance to these host compounds. In particular, expression of S. flexneri very-long O antigen (VL-Oag) LPS was found to play a central role in stress mitigation, as VL-Oag protects against antimicrobial FAs, but its presence rendered S. flexneri susceptible to DOC stress. Collectively, this work underpins the importance for S. flexneri to maintain appropriate regulation of cell envelope constituents, in particular VL-Oag LPS, to adequately adapt to diverse stresses during infection.

Original languageEnglish
Pages (from-to)1610-1621
Number of pages12
JournalACS Infectious Diseases
Volume9
Issue number8
Early online date26 Jul 2023
DOIs
Publication statusPublished - 11 Aug 2023

Keywords

  • bacterial cell envelope
  • deoxycholate
  • fatty acids
  • lipid homeostasis
  • lipopolysaccharide
  • Shigella flexneri

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