O'Boyle, N., Douce, G. R. , Farrell, G., Rattray, N. J. W., Schembri, M. A., Roe, A. J. and Connolly, J. P.R. (2023) Distinct ecological fitness factors coordinated by a conserved Escherichia coli regulator during systemic bloodstream infection. Proceedings of the National Academy of Sciences of the United States of America, 120(1), e2212175120. (doi: 10.1073/pnas.2212175120) (PMID:36574699) (PMCID:PMC9910484)
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Abstract
The ability of bacterial pathogens to adapt to host niches is driven by the carriage and regulation of genes that benefit pathogenic lifestyles. Genes that encode virulence or fitness-enhancing factors must be regulated in response to changing host environments to allow rapid response to challenges presented by the host. Furthermore, this process can be controlled by preexisting transcription factors (TFs) that acquire new roles in tailoring regulatory networks, specifically in pathogens. However, the mechanisms underlying this process are poorly understood. The highly conserved Escherichia coli TF YhaJ exhibits distinct genome-binding dynamics and transcriptome control in pathotypes that occupy different host niches, such as uropathogenic E. coli (UPEC). Here, we report that this important regulator is required for UPEC systemic survival during murine bloodstream infection (BSI). This advantage is gained through the coordinated regulation of a small regulon comprised of both virulence and metabolic genes. YhaJ coordinates activation of both Type 1 and F1C fimbriae, as well as biosynthesis of the amino acid tryptophan, by both direct and indirect mechanisms. Deletion of yhaJ or the individual genes under its control leads to attenuated survival during BSI. Furthermore, all three systems are up-regulated in response to signals derived from serum or systemic host tissue, but not urine, suggesting a niche-specific regulatory trigger that enhances UPEC fitness via pleiotropic mechanisms. Collectively, our results identify YhaJ as a pathotype-specific regulatory aide, enhancing the expression of key genes that are collectively required for UPEC bloodstream pathogenesis.
| Item Type: | Articles |
|---|---|
| Additional Information: | This work was supported by a Springboard award from the Academy of Medical Sciences [SBF005\1029] and a Research grant from the Royal Society [RGS\R2\202100] awarded to J.P.R.C., a Biotechnology and Biological Sciences Research Council grant awarded to A.J.R. [BB/R006539/1], and a Wellcome Trust Collaborative Award awarded to G.R.D. [204877/Z/16/Z]. |
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Roe, Professor Andrew and Connolly, Dr James and Douce, Dr Gillian |
| Authors: | O'Boyle, N., Douce, G. R., Farrell, G., Rattray, N. J. W., Schembri, M. A., Roe, A. J., and Connolly, J. P.R. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity |
| Journal Name: | Proceedings of the National Academy of Sciences of the United States of America |
| Publisher: | National Academy of Sciences |
| ISSN: | 0027-8424 |
| ISSN (Online): | 1091-6490 |
| Published Online: | 27 December 2022 |
| Copyright Holders: | Copyright © 2022 The Authors |
| First Published: | First published in Proceedings of the National Academy of Sciences of the United States of America 120(1): e2212175120 |
| Publisher Policy: | Reproduced under a Creative Commons License |
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