{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T02:09:52Z","timestamp":1791511792840,"version":"4.3.4"},"reference-count":104,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T00:00:00Z","timestamp":1771977600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:p>\n                    <jats:italic>Pseudomonas aeruginosa<\/jats:italic>\n                    is a multidrug-resistant Gram-negative nosocomial pathogen posing a major healthcare burden due to its intrinsic antibiotic resistance and environmental adaptability, which continue to significantly constrain therapeutic options. This pathogen is a leading cause of hospital-acquired respiratory and urinary tract infections that are often persistent and difficult to treat. The elucidation of metabolic adaptations permitting\n                    <jats:italic>P. aeruginosa<\/jats:italic>\n                    survival and supporting virulence in diverse host environments is essential for informing novel treatments. This study investigates the role of cytochrome\n                    <jats:italic>bc<\/jats:italic>\n                    <jats:sub>1<\/jats:sub>\n                    in\n                    <jats:italic>P. aeruginosa<\/jats:italic>\n                    PA14 growth, energetics, and virulence\n                    <jats:italic>in vitro<\/jats:italic>\n                    , under physiologically relevant conditions, and\n                    <jats:italic>in vivo<\/jats:italic>\n                    . The\n                    <jats:italic>bc<\/jats:italic>\n                    <jats:sub>1<\/jats:sub>\n                    deletion mutant exhibits significant growth defects in urinary- and lung-like media, demonstrating its importance in PA14 physiology, and displays reduced virulence in bladder epithelial cell monolayers, mediated by decreased type III secretion system (T3SS) toxin expression.\n                    <jats:italic>In vivo<\/jats:italic>\n                    , the mutant was nearly avirulent in a murine systemic infection model. Bioenergetic analysis revealed severe decline in PA14 \u0394\n                    <jats:italic>bc<\/jats:italic>\n                    <jats:sub>1<\/jats:sub>\n                    ATP production, aligning with the enzyme\u2019s central role in respiration and providing a mechanistic explanation for the mutant\u2019s reduced T3SS function, as toxin secretion requires energy. This work provides compelling evidence of direct T3SS regulation by cytochrome\n                    <jats:italic>bc<\/jats:italic>\n                    <jats:sub>1<\/jats:sub>\n                    , revealing a previously unrecognized link between respiratory metabolism and virulence. Metabolic profiling indicates that to compensate for cytochrome\n                    <jats:italic>bc<\/jats:italic>\n                    <jats:sub>1<\/jats:sub>\n                    loss, the mutant relies on NDH-2 and\n                    <jats:italic>bd<\/jats:italic>\n                    oxidase, permitting cellular survival but substantially reducing ATP yield. Collectively, these findings establish cytochrome\n                    <jats:italic>bc<\/jats:italic>\n                    <jats:sub>1<\/jats:sub>\n                    as a target for antibiotic development against\n                    <jats:italic>P. aeruginosa<\/jats:italic>\n                    , impacting bioenergetics, physiology, and virulence.\n                  <\/jats:p>","DOI":"10.3389\/fcimb.2026.1763669","type":"journal-article","created":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T07:04:27Z","timestamp":1772003067000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Essential role of cytochrome bc1 in Pseudomonas aeruginosa cell physiology and virulence"],"prefix":"10.3389","volume":"16","author":[{"given":"Jennifer M.","family":"Sorescu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mart\u00edn A.","family":"Gonz\u00e1lez-Montalvo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy","family":"Patel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriella","family":"Baltes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shriya R.","family":"Avula","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karina","family":"Tuz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oscar X.","family":"Ju\u00e1rez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,2,25]]},"reference":[{"key":"B1","first-page":"36","article-title":"Image processing with imageJ","volume":"11","author":"Abramoff","year":"2004","journal-title":"Biophotonics Int."},{"key":"B2","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1111\/j.1365-2958.2007.05772.x","article-title":"Responses of Pseudomonas aeruginosa to low oxygen indicate that growth in the cystic fibrosis lung is by aerobic respiration","volume":"65","author":"Alvarez-Ortega","year":"2007","journal-title":"Mol. 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