{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T16:40:28Z","timestamp":1777653628374,"version":"3.51.4"},"reference-count":77,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2015,4,1]],"date-time":"2015-04-01T00:00:00Z","timestamp":1427846400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2015,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            <jats:named-content content-type=\"genus-species\">Pseudomonas aeruginosa<\/jats:named-content>\n            is invasive or cytotoxic to host cells, depending on the type III secretion system (T3SS) effectors encoded. While the T3SS is known to be involved in disease\n            <jats:italic>in vivo<\/jats:italic>\n            , how it participates remains to be clarified. Here, mouse models of superficial epithelial injury (tissue paper blotting with EGTA treatment) and immunocompromise (MyD88 deficiency) were used to study the contribution of the T3SS transcriptional activator ExsA to epithelial traversal. Corneas of excised eyeballs were inoculated with green fluorescent protein (GFP)-expressing PAO1 or isogenic\n            <jats:italic>exsA<\/jats:italic>\n            mutants for 6 h\n            <jats:italic>ex vivo<\/jats:italic>\n            before bacterial traversal and epithelial thickness were quantified by using imaging. In the blotting-EGTA model,\n            <jats:italic>exsA<\/jats:italic>\n            mutants were defective in capacity for traversal. Accordingly, an \u223c16-fold variability in\n            <jats:italic>exsA<\/jats:italic>\n            expression among PAO1 isolates from three sources correlated with epithelial loss. In contrast, MyD88\n            <jats:sup>\u2212\/\u2212<\/jats:sup>\n            epithelia remained susceptible to\n            <jats:named-content content-type=\"genus-species\">P. aeruginosa<\/jats:named-content>\n            traversal despite\n            <jats:italic>exsA<\/jats:italic>\n            mutation. Epithelial lysates from MyD88\n            <jats:sup>\u2212\/\u2212<\/jats:sup>\n            mice had reduced antimicrobial activity compared to those from wild-type mice with and without prior antigen challenge, particularly 30- to 100-kDa fractions, for which mass spectrometry revealed multiple differences, including (i) lower baseline levels of histones, tubulin, and lumican and (ii) reduced glutathione\n            <jats:italic>S<\/jats:italic>\n            -transferase, annexin, and dermatopontin, after antigen challenge. Thus, the importance of ExsA in epithelial traversal by invasive\n            <jats:named-content content-type=\"genus-species\">P. aeruginosa<\/jats:named-content>\n            depends on the compromise enabling susceptibility, suggesting that strategies for preventing infection will need to extend beyond targeting the T3SS. The data also highlight the importance of mimicking conditions allowing susceptibility in animal models and the need to monitor variability among bacterial isolates from different sources, even for the same strain.\n          <\/jats:p>","DOI":"10.1128\/iai.02329-14","type":"journal-article","created":{"date-parts":[[2015,2,10]],"date-time":"2015-02-10T06:36:38Z","timestamp":1423550198000},"page":"1629-1640","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":26,"title":["The Importance of the Pseudomonas aeruginosa Type III Secretion System in Epithelium Traversal Depends upon Conditions of Host Susceptibility"],"prefix":"10.1128","volume":"83","author":[{"given":"Aaron B.","family":"Sullivan","sequence":"first","affiliation":[{"name":"School of Optometry, University of California, Berkeley, California, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K. P. 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