{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T21:50:16Z","timestamp":1768513816694,"version":"3.49.0"},"posted":{"date-parts":[[2024,6,25]]},"group-title":"Microbiology","reference-count":61,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,6,25]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  <jats:italic>Pseudomonas aeruginosa<\/jats:italic>\n                  (PA) is a gram-negative opportunistic pathogen that can infect the cornea as a result of trauma or contact lens wear. In addition to their known energy producing role, mitochondria are important mediators of immune signaling and host defense. While certain pathogens have developed strategies to evade host defenses by modulating host mitochondrial dynamics and metabolism, the ability of PA to harness host cell mitochondria during corneal infection is unknown. Using a combination of biochemical and imaging techniques, we show that PA infection of corneal epithelial cells induced mitochondrial fission in a DRP1-dependent manner that preceded PINK1\/Parkin and FUNDC1-mediated mitophagy. PA also impaired NADH-linked respiration through a reduction in complex 1. This corresponded to a decrease in metabolic pathways related to glycolysis and the TCA cycle. Metabolomics analysis further demonstrated an upregulation of the pentose phosphate pathway, arginine, purine, and pyrimidine metabolism in PA infected cells. These pathways may provide a key source of nucleotides, amino acids, and nitrogen for both the host cell and PA, in addition to antioxidant functions. Following treatment with gentamicin to kill all extracellular bacteria, metabolic flux analysis showed that corneal epithelial cells were able to restore mitochondrial function despite the continued presence of intracellular PA. Taken together, these data demonstrate that mitochondrial dysfunction and metabolic rewiring in host cells is triggered by extracellular PA, but once inside, PA requires healthy mitochondria to ensure host cell survival.\n                <\/jats:p>","DOI":"10.1101\/2024.06.24.600521","type":"posted-content","created":{"date-parts":[[2024,6,25]],"date-time":"2024-06-25T23:55:21Z","timestamp":1719359721000},"source":"Crossref","is-referenced-by-count":2,"title":["<i>Pseudomonas aeruginosa<\/i>\n                  impairs mitochondrial function and metabolism during infection of corneal epithelial cells"],"prefix":"10.64898","author":[{"given":"Rajalakshmy Ayilam","family":"Ramachandran","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joelle T.","family":"Abdallah","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mahad","family":"Rehman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hamid","family":"Baniasadi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abigail M.","family":"Blanton","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Santiago","family":"Vizcaino","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0136-2041","authenticated-orcid":false,"given":"Danielle M.","family":"Robertson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2024062615102108000_2024.06.24.600521v1.1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.04-0542"},{"key":"2024062615102108000_2024.06.24.600521v1.2","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.07-0993"},{"key":"2024062615102108000_2024.06.24.600521v1.3","doi-asserted-by":"publisher","DOI":"10.1097\/01.icl.0000177384.27778.4c"},{"key":"2024062615102108000_2024.06.24.600521v1.4","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.05-1332"},{"key":"2024062615102108000_2024.06.24.600521v1.5","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.02533-14"},{"key":"2024062615102108000_2024.06.24.600521v1.6","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00417-10"},{"key":"2024062615102108000_2024.06.24.600521v1.7","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01221-07"},{"key":"2024062615102108000_2024.06.24.600521v1.8","doi-asserted-by":"publisher","DOI":"10.1016\/j.micpath.2011.08.001"},{"key":"2024062615102108000_2024.06.24.600521v1.9","doi-asserted-by":"crossref","unstructured":"Andrieux P , Chevillard C , Cunha-Neto E , Nunes JPS . 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