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Lactobacillus crispatus Limits Bladder Uropathogenic E. coli Infection by Triggering a Host Type I Interferon Response.

Publication ,  Journal Article
Song, CH; Kim, YH; Naskar, M; Hayes, BW; Abraham, MA; Noh, JH; Suk, G; Kim, MJ; Cho, KS; Shin, M; Lee, E-J; Abraham, SN; Choi, HW
Published in: Proc Natl Acad Sci U S A
August 16, 2022

Many urinary tract infections (UTIs) are recurrent because uropathogens persist within the bladder epithelial cells (BECs) for extended periods between bouts of infection. Because persistent uropathogens are intracellular, they are often refractive to antibiotic treatment. The recent discovery of endogenous Lactobacillus spp. in the bladders of healthy humans raised the question of whether these endogenous bacteria directly or indirectly impact intracellular bacterial burden in the bladder. Here, we report that in contrast to healthy women, female patients experiencing recurrent UTIs have a bladder population of Lactobacilli that is markedly reduced. Exposing infected human BECs to L. crispatus in vitro markedly reduced the intracellular uropathogenic Escherichia coli (UPEC) load. The adherence of Lactobacilli to BECs was found to result in increased type I interferon (IFN) production, which in turn enhanced the expression of cathepsin D within lysosomes harboring UPECs. This lysosomal cathepsin D-mediated UPEC killing was diminished in germ-free mice and type I IFN receptor-deficient mice. Secreted metabolites of L. crispatus seemed to be responsible for the increased expression of type I IFN in human BECs. Intravesicular administration of Lactobacilli into UPEC-infected murine bladders markedly reduced their intracellular bacterial load suggesting that components of the endogenous microflora can have therapeutic effects against UTIs.

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Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

August 16, 2022

Volume

119

Issue

33

Start / End Page

e2117904119

Location

United States

Related Subject Headings

  • Uropathogenic Escherichia coli
  • Urinary Tract Infections
  • Urinary Bladder
  • Mice
  • Male
  • Lactobacillus crispatus
  • Interferon Type I
  • Immunity, Innate
  • Humans
  • Female
 

Citation

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Song, C. H., Kim, Y. H., Naskar, M., Hayes, B. W., Abraham, M. A., Noh, J. H., … Choi, H. W. (2022). Lactobacillus crispatus Limits Bladder Uropathogenic E. coli Infection by Triggering a Host Type I Interferon Response. Proc Natl Acad Sci U S A, 119(33), e2117904119. https://doi.org/10.1073/pnas.2117904119
Song, Chang Hyun, Young Ho Kim, Manisha Naskar, Byron W. Hayes, Mathew A. Abraham, Joo Hwan Noh, Gyeongseo Suk, et al. “Lactobacillus crispatus Limits Bladder Uropathogenic E. coli Infection by Triggering a Host Type I Interferon Response.Proc Natl Acad Sci U S A 119, no. 33 (August 16, 2022): e2117904119. https://doi.org/10.1073/pnas.2117904119.
Song CH, Kim YH, Naskar M, Hayes BW, Abraham MA, Noh JH, et al. Lactobacillus crispatus Limits Bladder Uropathogenic E. coli Infection by Triggering a Host Type I Interferon Response. Proc Natl Acad Sci U S A. 2022 Aug 16;119(33):e2117904119.
Song, Chang Hyun, et al. “Lactobacillus crispatus Limits Bladder Uropathogenic E. coli Infection by Triggering a Host Type I Interferon Response.Proc Natl Acad Sci U S A, vol. 119, no. 33, Aug. 2022, p. e2117904119. Pubmed, doi:10.1073/pnas.2117904119.
Song CH, Kim YH, Naskar M, Hayes BW, Abraham MA, Noh JH, Suk G, Kim MJ, Cho KS, Shin M, Lee E-J, Abraham SN, Choi HW. Lactobacillus crispatus Limits Bladder Uropathogenic E. coli Infection by Triggering a Host Type I Interferon Response. Proc Natl Acad Sci U S A. 2022 Aug 16;119(33):e2117904119.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

August 16, 2022

Volume

119

Issue

33

Start / End Page

e2117904119

Location

United States

Related Subject Headings

  • Uropathogenic Escherichia coli
  • Urinary Tract Infections
  • Urinary Bladder
  • Mice
  • Male
  • Lactobacillus crispatus
  • Interferon Type I
  • Immunity, Innate
  • Humans
  • Female