{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T12:31:57Z","timestamp":1787056317416,"version":"build-2736575974"},"reference-count":27,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:00:00Z","timestamp":1787011200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Objectives: This study aimed to explore the cellular injury phenotypes induced by outer membrane vesicles (OMVs) from uropathogenic Escherichia coli (E. coli, UPEC) and Proteus mirabilis (P. mirabilis, P. m) in human renal tubular epithelial HK-2 cells in vitro. Introduction: In urological practice, UPEC and P. mirabilis are representative pathogens of uncomplicated and complicated UTIs, respectively. Both are Gram-negative bacteria, and a notable feature of these bacteria is their ability to secrete OMVs. OMVs are nanoscale vesicles containing lipopolysaccharides (LPS), phospholipids, peptidoglycan, nucleic acids, and various virulence factors such as proteases and toxins. OMVs serve as effective carriers, delivering these toxic substances to host cells, triggering inflammatory responses, cellular damage, and ultimately cell death. Methods: In this study, we cultured standard pathogenic strains of E. coli and P. mirabilis in lysogeny broth (LB) medium until they reached the logarithmic growth phase. OMVs were isolated and identified. The uptake of OMVs by HK-2 cells was observed in vitro, and we evaluated the cytotoxic effects of both types of OMVs by measuring cell viability, oxidative stress, membrane permeability, mitochondrial function, and organelle morphology. Results: The results demonstrated that OMVs from both bacterial strains were efficiently internalized by HK-2 cells. Both OMVs induced oxidative stress, decreased antioxidant capacity, disrupted membrane permeability, and damaged mitochondrial function, leading to cell injury. Interestingly, while the two types of OMVs caused comparable cytotoxicity in terms of cell viability, oxidative stress and mitochondrial membrane potential, they produced distinct patterns of mitochondrial ultrastructural injury: P. mirabilis OMVs primarily caused mitochondrial structural deformation and blurred cristae, while E. coli OMVs led to mitochondrial swelling, cristae breakage, and vacuolization. These findings provide phenotypic evidence and experimental clues for understanding OMV-associated renal tubular epithelial injury caused by different uropathogens.<\/jats:p>","DOI":"10.3390\/pathogens15080859","type":"journal-article","created":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T12:09:32Z","timestamp":1787054972000},"page":"859","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Comparative Study of the Cytotoxic Effects of Outer Membrane Vesicles from Proteus mirabilis and Escherichia coli on HK-2 Cells"],"prefix":"10.3390","volume":"15","author":[{"given":"Qingchen","family":"Du","sequence":"first","affiliation":[{"name":"Department of Urology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua Medicine, Tsinghua University, Beijing 102218, China"},{"name":"Department of Urology, Qinghai University Affiliated Hospital, School of Clinical Medicine, Qinghai University, Xining 810000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xijie","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Urology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua Medicine, Tsinghua University, Beijing 102218, China"},{"name":"Department of Urology, Qinghai University Affiliated Hospital, School of Clinical Medicine, Qinghai University, Xining 810000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Endi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Urology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua Medicine, Tsinghua University, Beijing 102218, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyang","family":"Niu","sequence":"additional","affiliation":[{"name":"Department of Urology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua Medicine, Tsinghua University, Beijing 102218, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guojun","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Urology, Qinghai University Affiliated Hospital, School of Clinical Medicine, Qinghai University, Xining 810000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaoyue","family":"Ji","sequence":"additional","affiliation":[{"name":"Department of Urology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua Medicine, Tsinghua University, Beijing 102218, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiguo","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Urology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua Medicine, Tsinghua University, Beijing 102218, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1007\/s00345-021-03913-0","article-title":"Global, regional, and national burden of urinary tract infections from 1990 to 2019: An analysis of the global burden of disease study 2019","volume":"40","author":"Zeng","year":"2022","journal-title":"World J. 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