Gardnerella piotii enhances uropathogenic Escherichia coli infection through a succinate-GPR91-uroplakin axis.
7 affiliations
- 1Division of Life Sciences, Korea University, Seoul, 02841, South Korea.
- 2Department of Molecular Bioscience, Kangwon National University, Chuncheon, 24341, South Korea.
- 3Multidimensional Genomics Research Center, Kangwon National University, Chuncheon, 24341, South Korea.
- 4Department of Laboratory Medicine and Genetics, Soonchunhyang University Bucheon Hospital, Bucheon, 14584, South Korea.
- 5Division of Life Sciences, Korea University, Seoul, 02841, South Korea. [email protected].
- 6National Research Laboratory for Convergence Degradation Biology, Korea University, Seoul, 02841, South Korea. [email protected].
- 7Department of Urology, Soonchunhyang University Bucheon Hospital, Bucheon, 14584, South Korea. [email protected].
Abstract
Background
Uropathogenic Escherichia coli (UPEC) is the principal causative agent of urinary tract infections (UTIs); however, urine samples from patients with recurrent cystitis frequently harbor diverse coexisting bacterial taxa. How such polymicrobial urobiota can functionally modulate bladder susceptibility to UPEC infection remains unclear.Results
We integrated 16S rRNA-based microbiota profiling of a recurrent cystitis cohort with mechanistic in vitro and in vivo models to assess host-microbe interactions within the urinary tract. We identified Gardnerella piotii as a microbial modifier that enhances the infectivity of UPEC without inducing overt epithelial damage or inflammation. Exposure to G. piotii increased UPEC burden in the bladder and in bladder epithelial cells by promoting early bacterial adhesion. Mechanistically, G. piotii actively produced succinate, which acted as a host-active metabolite to selectively upregulate uroplakin expression through signaling via the succinate receptor GPR91. Genetic ablation of GPR91 abolished succinate- and G. piotii-induced uroplakin upregulation and UPEC adhesion, establishing that this epithelial signaling axis is necessary for infection sensitization. Importantly, the heightened UPEC susceptibility induced by G. piotii could be partially mitigated; introduction of the beneficial commensal Lactobacillus crispatus or exposure to lactate partially reduced UPEC burden in vivo, highlighting the functional plasticity of the bladder microenvironment.Conclusions
These findings unravel a metabolite-driven mechanism by which members of the urinary microbiota modulate host epithelial programs to influence UPEC infection. By identifying a succinate-GPR91-uroplakin signaling axis that links polymicrobial community structure to epithelial susceptibility, our study reframes recurrent cystitis as a dynamic ecological process shaped by microbial existence and metabolic signaling rather than by an individual pathogen. Video Abstract.
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BibTeX
@article{lee2026gardnerella,
title = {{Gardnerella piotii enhances uropathogenic Escherichia coli infection through a succinate-GPR91-uroplakin axis.}},
author = {Ho Young Lee and Min Jung Kim and Manisha Naskar and Karen Serrano-Arevalo and Yong-Joon Cho and Hee Bong Shin and Hae Woong Choi and Young Ho Kim},
journal = {Microbiome},
year = {2026},
month = aug,
doi = {10.1186/s40168-026-02499-2},
url = {https://europepmc.org/article/MED/42968172},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Gardnerella piotii enhances uropathogenic Escherichia coli infection through a succinate-GPR91-uroplakin axis.
AU - Ho Young Lee
AU - Min Jung Kim
AU - Manisha Naskar
AU - Karen Serrano-Arevalo
AU - Yong-Joon Cho
AU - Hee Bong Shin
AU - Hae Woong Choi
AU - Young Ho Kim
PY - 2026
DA - 2026/08/05
JO - Microbiome
DO - 10.1186/s40168-026-02499-2
UR - https://europepmc.org/article/MED/42968172
AB - Background Uropathogenic Escherichia coli (UPEC) is the principal causative agent of urinary tract infections (UTIs); however, urine samples from patients with recurrent cystitis frequently harbor diverse coexisting bacterial taxa. How such polymicrobial urobiota can functionally modulate bladder susceptibility to UPEC infection remains unclear.Results We integrated 16S rRNA-based microbiota profiling of a recurrent cystitis cohort with mechanistic in vitro and in vivo models to assess host-microbe interactions within the urinary tract. We identified Gardnerella piotii as a microbial modifier that enhances the infectivity of UPEC without inducing overt epithelial damage or inflammation. Exposure to G. piotii increased UPEC burden in the bladder and in bladder epithelial cells by promoting early bacterial adhesion. Mechanistically, G. piotii actively produced succinate, which acted as a host-active metabolite to selectively upregulate uroplakin expression through signaling via the succinate receptor GPR91. Genetic ablation of GPR91 abolished succinate- and G. piotii-induced uroplakin upregulation and UPEC adhesion, establishing that this epithelial signaling axis is necessary for infection sensitization. Importantly, the heightened UPEC susceptibility induced by G. piotii could be partially mitigated; introduction of the beneficial commensal Lactobacillus crispatus or exposure to lactate partially reduced UPEC burden in vivo, highlighting the functional plasticity of the bladder microenvironment.Conclusions These findings unravel a metabolite-driven mechanism by which members of the urinary microbiota modulate host epithelial programs to influence UPEC infection. By identifying a succinate-GPR91-uroplakin signaling axis that links polymicrobial community structure to epithelial susceptibility, our study reframes recurrent cystitis as a dynamic ecological process shaped by microbial existence and metabolic signaling rather than by an individual pathogen. Video Abstract.
SN - 2049-2618
ER -