OSCR

Bladder mucosal afferents detect UTI and aid pathogen clearance.

Overview

Authors: Cindy Tay1, Harman Sharma1, Stewart Ramsay2,3, Georgia Bourlotos1, Sarah K. Manning1,4, Natalie E. Stevens1,5, Sophie J. Miller1,4, Geraint B. Rogers1,4, David J. Lynn1,5, Feargal J. Ryan1,5, Andrea M. Harrington6,7, Vladimir Zagorodnyuk1, Steven L. Taylor1,4, Luke Grundy1
ORCID iDs: Cindy Tay, Natalie E. Stevens, Sophie J. Miller, Feargal J. Ryan, Andrea M. Harrington, Vladimir Zagorodnyuk, Steven L. Taylor, Luke Grundy
  1. College of Medicine and Public Health, Flinders Health and Medical Research Institute, Flinders University, Bedford Park, SA 5042, Australia
  2. Lifelong Health, South Australian Health and Medical Research Institute, Adelaide, SA 5000, Australia
  3. Adelaide Medical School, The University of Adelaide, Adelaide, SA 5000, Australia
  4. Microbiome and Host Health Programme, South Australian Health and Medical Research Institute, Adelaide, SA 5000, Australia
  5. Precision Cancer Medicine Theme, South Australian Health and Medical Research Institute, Adelaide, SA 5000, Australia
  6. Visceral Pain Research Group, Hopwood Centre for Neurobiology, Lifelong Health Theme, South Australian Health and Medical Research Institute, Adelaide, SA 5000, Australia
  7. School of Biomedicine, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, SA 5005, Australia
Institutions: Flinders University (Australia); South Australian Health and Medical Research Institute (Australia)
Journal: Proceedings of the National Academy of Sciences of the United States of America, volume 123, issue 32, article e2604124123
Dates: received 9 February 2026; accepted 23 June 2026; published online 3 August 2026; in print 11 August 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1073/pnas.2604124123 · PMID 42546184 · PMCID PMC13462357 · OpenAlex W4415533023
Open access: hybrid, a free copy (OpenAlex)
Preprint: doi:10.1101/2025.10.23.684249
Status: code on request
Categories: mouse (organism), other condition (population), pain (population)
Methods: Spectral & time-frequency, Statistics
Keywords: urinary tract infection, bladder afferent, cystitis, pain, infection
MeSH: Escherichia coli Infections*, Mucous Membrane*, Neurons, Afferent*, Urinary Bladder*, Urinary Tract Infections*, Animals, Disease Models, Animal, Diterpenes, Female, Mice, Mice, Inbred C57BL, Uropathogenic Escherichia coli (* major topic)
Journal subjects: Biological Sciences, Neuroscience
Topic: Urinary Tract Infections Management (Epidemiology, Medicine), according to OpenAlex
Funding: National Health and Medical Research Council (2008625, 2017404); Flinders Foundation (Health Seed Grant); Australian Research Council (DP260100487)
Citations: not cited yet (Europe PMC); 86 references in the paper

Abstract

The bladder is innervated by a complex network of sensory neurons that detect and transmit mechanical and chemical signals to the central nervous system, regulating both urine storage and voiding, and mediating sensations of bladder fullness and pain. While stretch-sensitive afferents within the bladder wall are known to monitor bladder tension, the contribution of stretch-insensitive afferents that reside within the bladder mucosa to bladder sensation and function remains unclear. Here, we establish a mouse model of selective bladder mucosal afferent denervation using intravesical instillation of resiniferatoxin to define the functional roles of these fibers in health and disease. We assessed the impact of mucosal denervation on sensory nerve activity and bladder function in healthy mice and in a model of urinary tract infection (UTI) induced by acute bacterial challenge with uropathogenic Escherichia coli. We show that mucosa-innervating afferents do not influence bladder distension responses or voiding function under healthy conditions. In contrast, during UTI, these afferents become hypersensitive and serve as important drivers of infection-induced pelvic pain and urinary frequency, responses that contribute to bacterial clearance. Together, these findings identify bladder mucosal afferents as key sensors of pathogenic challenge and reveal a previously unrecognized mechanism that drives behavioral responses to reduce the burden and extent of UTI.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

The paper says that its authors' code is available on request: it was not published with the paper, so there is nothing to verify.

The paper's code and data availability statement is in the Data section.

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Data

No dataset and no data link were found in the paper.

Data, Materials, and Software Availability

Reagents used here will be shared upon reasonable request to the corresponding author. All other study data are provided in the article or SI Appendix (http://www.pnas.org/lookup/doi/10.1073/pnas.2604124123#supplementary-materials).

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 14 authors, 5 keywords, 12 MeSH terms, 3 funders, 86 references.

Cite

This paper

Tay, C., Sharma, H., Ramsay, S., Bourlotos, G., Manning, S. K., Stevens, N. E., Miller, S. J., Rogers, G. B., Lynn, D. J., Ryan, F. J., Harrington, A. M., Zagorodnyuk, V., Taylor, S. L., & Grundy, L. (2026). Bladder mucosal afferents detect UTI and aid pathogen clearance. Proceedings of the National Academy of Sciences of the United States of America, 123(32), e2604124123. https://doi.org/10.1073/pnas.2604124123

BibTeX

@article{tay2026bladder,
author = {Tay, Cindy and Sharma, Harman and Ramsay, Stewart and Bourlotos, Georgia and Manning, Sarah K. and Stevens, Natalie E. and Miller, Sophie J. and Rogers, Geraint B. and Lynn, David J. and Ryan, Feargal J. and Harrington, Andrea M. and Zagorodnyuk, Vladimir and Taylor, Steven L. and Grundy, Luke},
title = {{Bladder mucosal afferents detect UTI and aid pathogen clearance}},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
year = {2026},
month = aug,
volume = {123},
number = {32},
pages = {e2604124123},
publisher = {National Academy of Sciences},
issn = {0027-8424},
doi = {10.1073/pnas.2604124123},
url = {https://doi.org/10.1073/pnas.2604124123},
pmid = {42546184},
pmcid = {PMC13462357}
}

RIS

TY - JOUR
AU - Tay, Cindy
AU - Sharma, Harman
AU - Ramsay, Stewart
AU - Bourlotos, Georgia
AU - Manning, Sarah K.
AU - Stevens, Natalie E.
AU - Miller, Sophie J.
AU - Rogers, Geraint B.
AU - Lynn, David J.
AU - Ryan, Feargal J.
AU - Harrington, Andrea M.
AU - Zagorodnyuk, Vladimir
AU - Taylor, Steven L.
AU - Grundy, Luke
TI - Bladder mucosal afferents detect UTI and aid pathogen clearance
T2 - Proceedings of the National Academy of Sciences of the United States of America
J2 - Proc Natl Acad Sci U S A
PY - 2026
DA - 2026/08/03
VL - 123
IS - 32
SP - e2604124123
SN - 0027-8424
PB - National Academy of Sciences
DO - 10.1073/pnas.2604124123
UR - https://doi.org/10.1073/pnas.2604124123
LA - en
ER -

CSL-JSON

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