Distinct intraspecies virulence mechanisms regulated by a conserved transcription factor

James P R Connolly, Nicky O'Boyle, Natasha C A Turner, Douglas F Browning, Andrew J Roe

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)19695-19704
Number of pages10
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number39
Publication statusPublished - 24 Sept 2019

Bibliographical note

Copyright © 2019 the Author(s). Published by PNAS. This open access article is distributed under Creative Commons Attribution License 4.0 (CC BY).


  • 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


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