Genomic plasticity of pathogenic Escherichia coli mediates D-serine tolerance via multiple adaptive mechanisms

Nicky O'Boyle, James P. R. Connolly, Nicholas P. Tucker, Andrew J. Roe

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)
9 Downloads (Pure)

Abstract

The molecular environment of the host can have profound effects on the behavior of resident bacterial species. We recently established how the sensing and response of enterohemorrhagic Escherichia coli (EHEC) to D-serine (D-Ser) resulted in down-regulation of type 3 secretion system-dependent colonization, thereby avoiding unfavorable environments abundant in this toxic metabolite. However, this model ignores a key determinant of the success of bacterial pathogens, adaptive evolution. In this study, we have explored the adaptation of EHEC to D-Ser and its consequences for pathogenesis. We rapidly isolated multiple, independent, EHEC mutants whose growth was no longer compromised in the presence of D-Ser. Through a combination of whole-genome sequencing and transcriptomics, we showed that tolerance could be attributed to disruption of one of two D-Ser transporters and/or activation of a previously nonfunctional D-Ser deaminase. While the implication of cytoplasmic transport in D-Ser toxicity was unsurprising, disruption of a single transporter, CycA, was sufficient to completely overcome the repression of type 3 secretion system activity normally associated with exposure to D-Ser. Despite the fact that this reveals a mechanism by which evolution could drive a pathogen to colonize new niches, interrogation of sequenced E. coli O157:H7 genomes showed a high level of CycA conservation, highlighting a strong selective pressure for functionality. Collectively, these data show that CycA is a critically important conduit for D-Ser uptake that is central to the niche restriction of EHEC.

Original languageEnglish
Pages (from-to)22484-22493
Number of pages10
JournalProceedings of the National Academy of Sciences of the United States of America
Volume117
Issue number36
Early online date26 Aug 2020
DOIs
Publication statusPublished - 8 Sep 2020

Keywords

  • D-serine
  • Escherichia coli
  • pathogens

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