Roles of inflammatory processes and the vaginal microbiome in host susceptibility to urinary tract infection
Infections of the urinary tract have been linked with adverse pregnancy outcomes and decreased quality of life for women who suffer common recurrences. Clinical evidence suggests roles for the vaginal microbiota in determining susceptibility to urinary tract infection (UTI), the most common cause of which is Escherichia coli. However, there is little understanding about how crosstalk between the vaginal and urinary tract microbiomes influences UTI. We developed a mouse model of recurrent UTI in which we demonstrated that E. coli harbored within bladder tissue reservoirs emerged in response to exposures to Gardnerella (but not healthy lactobacilli) to cause recurrent UTI. This model attempts to understand the effects of urinary tract exposures to vaginal bacteria and may help to explain clinical associations between BV and UTI and the experience of recurrent postcoital UTI.
Model of Gardnerella covert pathogenesis in recurrent UTI
In women, approximately half of recurrent urinary tract infection (rUTI) episodes are caused by an E. coli strain identical to the strain that caused the initial infection. Here we present a model of one mechanism of rUTI: activation of latent intracellular E. coli reservoirs in the bladder. Our data in mice suggest that Gardnerella urinary tract exposure, likely a consequence of sexual activity, results in exfoliation of the bladder epithelium and damage to the kidney. Subsequent to exfoliation, E. coli emerges from intracellular reservoirs into the bladder lumen, where it can ascend into the kidney, sometimes causing severe inflammation and systemic infection. Often E. coli rUTI occurs after Gardnerella clearance from the urinary tract. These findings have important implications for our understanding of rUTI etiology and point to Gardnerella colonization as a potentially important marker of rUTI risk.
Gilbert NM, O'Brien VP, Lewis AL. Transient microbiota exposures activate dormant Escherichia coli infection in the bladder and drive severe outcomes of recurrent disease. PLoS Pathog. 2017 Mar 30;13(3):e1006238. doi: 10.1371/journal.ppat.1006238. eCollection 2017 Mar. PMID: 28358889. PMCID: PMC5373645
Other publications on vaginal microbiome and UTI
Kline, KA; Lewis, AL. Gram-Positive Uropathogens, Polymicrobial Urinary Tract Infection, and the Emerging Microbiota of the Urinary Tract. Microbiology Spectrum. 2016, March 11; 4(2) PMID: 27227294 PMCID: PMC4888879
Kline, K.A.; Schwartz, D.J.; Gilbert, NM; Hultgren, S.J.; Lewis, A.L. Immune Modulation by Group B Streptococcus Influences Host Susceptibility to Urinary Tract Infection by Uropathogenic E. coli. Infect. Immun. 2012 Dec;80(12):4186-94. PMID 22988014 PMCID: PMC3497425
Kline, K.A.; Schwartz, D.J.; Gilbert, NM; Lewis, A.L. Impact of Host Age and Parity on Susceptibility to Severe Urinary Tract Infection in a Murine Model. PLoS One. 2014 May 16;9(5):e97798. PMID: 24835885
O'Brien VP, Hannan TJ, Yu L, Livny J, Roberson ED, Schwartz DJ, Souza S, Mendelsohn CL, Colonna M, Lewis AL, Hultgren SJ. A Mucosal Imprint left by Prior Escherichia coli Bladder Infection Sensitizes to Recurrent Disease. Nat Microbiol. 2016 Oct;2:16196 PMID: 27798558. PMCID: PMC5308540
O'Brien VP, Joens MS, Lewis AL, Gilbert NM. Recurrent Escherichia coli Urinary Tract Infection Triggered by Gardnerella vaginalis Bladder Exposure in Mice. J Vis Exp. 2020 Dec 4;(166). doi: 10.3791/61967. PubMed PMID: 33346201; PubMed Central PMCID: PMC8034409
Gilbert NM, Choi B, Du J, Collins C, Lewis AL, Putonti C, Wolfe AJ. A mouse model displays host and bacterial strain differences in Aerococcus urinae urinary tract infection. Biol Open. 2021 Aug 15;10(8). doi: 10.1242/bio.058931. Epub 2021 Aug 13. PubMed PMID: 34387311; PubMed Central PMCID: PMC8380466.
O'Brien VP, Lewis AL, Gilbert NM. Bladder Exposure to Gardnerella Activates Host Pathways Necessary for Escherichia coli Recurrent UTI. Front Cell Infect Microbiol. 2021 Dec 6;11:788229. doi: 10.3389/fcimb.2021.788229. eCollection 2021. PMID: 34938672
Gilbert NM, O'Brien VP, Waller C, Batourina E, Mendelsohn CL, Lewis AL. Gardnerella Exposures Alter Bladder Gene Expression and Augment Uropathogenic Escherichia coli Urinary Tract Infection in Mice. Front Cell Infect Microbiol. 2022 Jun 16;12:909799. doi: 10.3389/fcimb.2022.909799. eCollection 2022.PMID: 35782131
Scanning electron micrograph of the inner surface of the bladder,
illustrating an exfoliated area after