The Vaginal Microbiome

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 provided the first proof of principle in an animal model that a member of the vaginal microbiota (Group B Streptococcus, GBS), when part of the inoculum that reaches the urinary tract, can influence the outcome of E. coli UTI. Mechanistic work suggests that the GBS capsular polysaccharide modulates the host immune response in a manner that benefits both itself and co-infecting E. coli. We have also contributed to mounting evidence showing that improper inflammatory responses can drive enhanced host susceptibility to more severe forms of 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.

  1. 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

  2. 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

  3. 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

  4. 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

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Scanning electron micrograph of the inner surface of the bladder,

illustrating an exfoliated area after