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Copper affects virulence and diverse phenotypes of uropathogenic Proteus mirabilis

Authors :
Wei-Syuan Huang
Yuan-Ju Lee
Lu Wang
Hsuan- Hsuan Chen
Yueh-Jung Chao
Vivien Cheng
Shwu-Jen Liaw
Source :
Journal of Microbiology, Immunology and Infection, Vol 57, Iss 3, Pp 385-395 (2024)
Publication Year :
2024
Publisher :
Elsevier, 2024.

Abstract

Background: Copper plays a role in urinary tract infection (UTI) and urinary copper content is increased during Proteus mirabilis UTI. We therefore investigated the effect of copper on uropathogenic P. mirabilis and the underlying mechanisms, focusing on the virulence associated aspects. Methods: Mouse colonization, swarming/swimming assays, measurement of cell length, flagellin level and urease activity, adhesion/invasion assay, biofilm formation, killing by macrophages, oxidative stress susceptibility, OMPs analysis, determination of MICs and persister cell formation, RT-PCR and transcriptional reporter assay were performed. Results: We found that copper-supplemented mice were more resistant to be colonized in the urinary tract, together with decreased swarming/swimming, ureases activity, expression of type VI secretion system and adhesion/invasion to urothelial cells and increased killing by macrophages of P. mirabilis at a sublethal copper level. However, bacterial biofilm formation and resistance to oxidative stress were enhanced under the same copper level. Of note, the presence of copper led to increased ciprofloxacin MIC and more persister cell formation against ampicillin. In addition, the presence of copper altered the outer membrane protein profile and triggered expression of RcsB response regulator. For the first time, we unveiled the pleiotropic effects of copper on uropathogenic P. mirabilis, especially for induction of bacterial two-component signaling system regulating fitness and virulence. Conclusion: The finding of copper-mediated virulence and fitness reinforced the importance of copper for prevention and therapeutic interventions against P. mirabilis infections. As such, this study could facilitate the copper-based strategies against UTI by P. mirabilis.

Details

Language :
English
ISSN :
16841182
Volume :
57
Issue :
3
Database :
Directory of Open Access Journals
Journal :
Journal of Microbiology, Immunology and Infection
Publication Type :
Academic Journal
Accession number :
edsdoj.2cd4c02f4d964a6e8acde673167dcfa9
Document Type :
article
Full Text :
https://doi.org/10.1016/j.jmii.2024.02.007