{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T23:37:00Z","timestamp":1790638620986,"version":"4.1.0"},"reference-count":43,"publisher":"National Academy of Sciences","issue":"48","license":[{"start":{"date-parts":[[2020,5,11]],"date-time":"2020-05-11T00:00:00Z","timestamp":1589155200000},"content-version":"vor","delay-in-days":182,"URL":"https:\/\/www.pnas.org\/site\/aboutpnas\/licenses.xhtml"}],"funder":[{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI135453"],"award-info":[{"award-number":["AI135453"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2019,11,26]]},"abstract":"<jats:p>\n                    An earlier report described a human case of necrotizing fasciitis (NF) caused by mixed infection with 4\n                    <jats:italic>Aeromonas hydrophila<\/jats:italic>\n                    strains (NF1\u2013NF4). While the NF2, NF3, and NF4 strains were clonal and possessed exotoxin A (ExoA), the NF1 strain was determined to be phylogenetically distinct, harboring a unique type 6 secretion system (T6SS) effector (TseC). During NF1 and NF2 mixed infection, only NF1 disseminated, while NF2 was rapidly killed by a contact-dependent mechanism and macrophage phagocytosis, as was demonstrated by using in vitro models. To confirm these findings, we developed 2 NF1 mutants (NF1\u0394\n                    <jats:italic>tseC<\/jats:italic>\n                    and NF1\u0394\n                    <jats:italic>vasK<\/jats:italic>\n                    );\n                    <jats:italic>vasK<\/jats:italic>\n                    encodes an essential T6SS structural component. NF1 VasK and TseC were proven to be involved in contact-dependent killing of NF2 in vitro, as well as in its elimination at the intramuscular injection site in vivo during mixed infection, with overall reduced mouse mortality. ExoA was shown to have an important role in NF by both NF1-\n                    <jats:italic>exoA<\/jats:italic>\n                    (with\n                    <jats:italic>cis exoA<\/jats:italic>\n                    ) and NF2 during monomicrobial infection. However, the contribution of ExoA was more important for NF2 than NF1 in the murine peritonitis model. The NF2\u2206\n                    <jats:italic>exoA<\/jats:italic>\n                    mutant did not significantly alter animal mortality or NF1 dissemination during mixed infection in the NF model, suggesting that the ExoA activity was significant at the injection site. Immunization of mice to ExoA protected animals from NF2 monomicrobial challenge, but not from polymicrobial infection because of NF2 clearance. This study clarified the roles of T6SS and ExoA in pathogenesis caused by\n                    <jats:italic>A. hydrophila<\/jats:italic>\n                    NF strains in both mouse peritonitis and NF models in monomicrobial and polymicrobial infections.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1914395116","type":"journal-article","created":{"date-parts":[[2019,11,11]],"date-time":"2019-11-11T20:25:26Z","timestamp":1573503926000},"page":"24084-24092","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":28,"title":["T6SS and ExoA of flesh-eating\n                    <i>Aeromonas hydrophila<\/i>\n                    in peritonitis and necrotizing fasciitis during mono- and polymicrobial infections"],"prefix":"10.1073","volume":"116","author":[{"given":"Ana","family":"Fern\u00e1ndez-Bravo","sequence":"first","affiliation":[{"name":"Unidad de Microbiolog\u00eda, Departamento de Ciencias M\u00e9dicas B\u00e1sicas, Facultad de Medicina y Ciencias de la Salud, Instituto de Investigaci\u00f3n Sanitaria Pere Virgili, Universidad Rovira i Virgili, 43201 Reus, Spain;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul B.","family":"Kilgore","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, 77555;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jourdan A.","family":"Andersson","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, 77555;"},{"name":"Department of Pathology and Immunology and Texas Children\u2019s Microbiome Center, Baylor College of Medicine, Houston, TX, 77030;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Blears","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, 77555;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Jos\u00e9","family":"Figueras","sequence":"additional","affiliation":[{"name":"Unidad de Microbiolog\u00eda, Departamento de Ciencias M\u00e9dicas B\u00e1sicas, Facultad de Medicina y Ciencias de la Salud, Instituto de Investigaci\u00f3n Sanitaria Pere Virgili, Universidad Rovira i Virgili, 43201 Reus, Spain;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nur A.","family":"Hasan","sequence":"additional","affiliation":[{"name":"Research and Development Department, CosmosID Inc., Rockville, MD 20850;"},{"name":"Center for Bioinformatics and Computational Biology, University of Maryland Institute for Advanced Computer Studies, University of Maryland, College Park, MD 20742;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rita R.","family":"Colwell","sequence":"additional","affiliation":[{"name":"Research and Development Department, CosmosID Inc., Rockville, MD 20850;"},{"name":"Center for Bioinformatics and Computational Biology, University of Maryland Institute for Advanced Computer Studies, University of Maryland, College Park, MD 20742;"},{"name":"Bloomberg School of Public Health, The Johns Hopkins University, Baltimore, MD 21205"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Sha","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, 77555;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashok K.","family":"Chopra","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, 77555;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2019,11,11]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1073\/pnas.1523817113","article-title":"Cross-talk among flesh-eating Aeromonas hydrophila strains in mixed infection leading to necrotizing fasciitis","volume":"113","author":"Ponnusamy D.","year":"2016","unstructured":"D. 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