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

Lookup NU author(s): Dr James ConnollyORCiD



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


© 2020 National Academy of Sciences. All rights reserved.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.

Publication metadata

Author(s): O'Boyle N, Connolly JPR, Tucker NP, Roe AJ

Publication type: Article

Publication status: Published

Journal: Proceedings of the National Academy of Sciences of the United States of America

Year: 2020

Volume: 117

Issue: 36

Pages: 22484-22493

Print publication date: 08/09/2020

Online publication date: 26/08/2020

Acceptance date: 28/07/2020

Date deposited: 16/12/2020

ISSN (print): 0027-8424

ISSN (electronic): 1091-6490

Publisher: National Academy of Sciences


DOI: 10.1073/pnas.2004977117

PubMed id: 32848072


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Funder referenceFunder name
Biological Sciences Research Council funding (BB/R006539/1) awarded to A.J.R.
This work was supported by a Tenovus Scotland Small Pilot Grant awarded to N.O.