Distinct intraspecies virulence mechanisms regulated by a conserved transcription factor

Abstract

Tailoring transcriptional regulation to coordinate the expression of virulence factors in tandem with the core genome is a hallmark of bacterial pathogen evolution. Bacteria encode hundreds of transcription factors forming the base-level control of gene regulation. Moreover, highly homologous regulators are assumed to control conserved genes between members within a species that harbor the same genetic targets. We have explored this concept in 2 Escherichia coli pathotypes that employ distinct virulence mechanisms that facilitate specification of a different niche within the host. Strikingly, we found that the transcription factor YhaJ actively regulated unique gene sets between intestinal enterohemorrhagic E. coli (EHEC) and extraintestinal uropathogenic E. coli (UPEC), despite being very highly conserved. In EHEC, YhaJ directly activates expression of type 3 secretion system components and effectors. Alternatively, YhaJ enhances UPEC virulence regulation by binding directly to the phase-variable type 1 fimbria promoter, driving its expression. Additionally, YhaJ was found to override the universal GAD acid tolerance system but exclusively in EHEC, thereby indirectly enhancing type 3 secretion pleiotropically. These results have revealed that within a species, conserved regulators are actively repurposed in a "personalized" manner to benefit particular lifestyles and drive virulence via multiple distinct mechanisms.

Publication DOI: https://doi.org/10.1073/pnas.1903461116
Divisions: College of Health & Life Sciences > School of Biosciences
Additional Information: Copyright © 2019 the Author(s). Published by PNAS. This open access article is distributed under Creative Commons Attribution License 4.0 (CC BY).
Uncontrolled Keywords: Bacteria/genetics,Enterohemorrhagic Escherichia coli/genetics,Escherichia coli/genetics,Escherichia coli Infections/microbiology,Escherichia coli Proteins/metabolism,Fimbriae, Bacterial/genetics,Gene Expression Regulation, Bacterial/genetics,Transcription Factors/genetics,Type III Secretion Systems/genetics,Uropathogenic Escherichia coli/metabolism,Virulence/genetics,Virulence Factors/genetics
Publication ISSN: 1091-6490
Last Modified: 08 Jul 2024 08:09
Date Deposited: 17 Jan 2022 11:15
Full Text Link:
Related URLs: https://www.pna ... nt/116/39/19695 (Publisher URL)
PURE Output Type: Article
Published Date: 2019-09-24
Accepted Date: 2019-08-15
Authors: Connolly, James P R
O'Boyle, Nicky
Turner, Natasha C A
Browning, Douglas F (ORCID Profile 0000-0003-4672-3514)
Roe, Andrew J

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