Quorum sensing modulates bacterial virulence and colonization dynamics of the gastrointestinal pathogen Citrobacter rodentium

ABSTRACT

Quorum Sensing (QS) is a form of cell-to-cell communication that enables bacteria to modify behavior according to their population density. While QS has been proposed as a potential intervention against pathogen infection, QS-mediated communication within the mammalian digestive tract remains understudied. Using an LC-MS/MS approach, we discovered that Citrobacter rodentium, a natural murine pathogen used to model human infection by pathogenic Escherichia coli, utilizes the CroIR system to produce three QS-molecules. We then profiled their accumulation both in vitro and across different gastrointestinal sites over the course of infection. Importantly, we found that in the absence of QS capabilities the virulence of C. rodentium is enhanced. This highlights the role of QS as an effective mechanism to regulate virulence according to the pathogen’s spatio-temporal context to optimize colonization and transmission success. These results also demonstrate that inhibiting QS may not always be an effective strategy for the control of virulence.

KEYWORDS:

• Quorum sensing
• bacterial communication
• AHLs
• autoinducers
• chemical signaling
• RNA-seq
• bacterial attachment
• virulence
• type III secretion system
• pathogenesis

Acknowledgments

The authors would like to thank all of our colleagues in the Finlay laboratory for their support and assistance. B.B.F. is a University of British Columbia Peter Wall Distinguished Professor. J Peña-Díaz received support from the University of British Columbia (UBC) and from Mitacs. Supporting images were created with BioRender (BioRender.com). This research was enabled in part by software provided by the Digital Research Alliance of Canada (alliancecan.ca). We are grateful to Matthew Croxen and Kirsten Koymans for generating the DBS100 ∆croI mutant. We would also like to thank Lisa Thorson for the fundamental logistical support of the project.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Author contributions

J.P.D. and B.B.F conceived the project. J.P.D., S.E.W., A.S.P., A.C.C., W.D., and S.O.J. performed and designed experiments. J.P.D., S.E.W., and A.C.C., analyzed data. J.P.D. wrote bioinformatics pipelines. J.P.D. wrote the original draft of the manuscript with input from all authors. All authors revised the manuscript. B.B.F. acquired funding for the project and provided supervision.

Data availability statement

RNA-seq data generated from this study are available on the NCBI Sequence Read Archive (SRA) under the BioProject accession number PRJNA935367. The source data as well as any additional information necessary for the reanalysis of the data reported in this paper are available from the corresponding author upon reasonable request.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/19490976.2023.2267189

Additional information

Funding

This work was supported by grants from the Canadian Institutes of Health Research (CIHR) to BB Finlay [FDN-159935].