Distinct intraspecies virulence mechanisms regulated by a conserved transcription factor

19Citations
Citations of this article
51Readers
Mendeley users who have this article in their library.

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.

Cite

CITATION STYLE

APA

Connolly, J. P. R., O’Boyle, N., Turner, N. C. A., Browning, D. F., & Roe, A. J. (2019). Distinct intraspecies virulence mechanisms regulated by a conserved transcription factor. Proceedings of the National Academy of Sciences of the United States of America, 116(39), 19695–19704. https://doi.org/10.1073/pnas.1903461116

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free