{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T15:09:26Z","timestamp":1784128166464,"version":"3.55.0"},"reference-count":55,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2022,10,20]],"date-time":"2022-10-20T00:00:00Z","timestamp":1666224000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/doi.org\/10.1128\/ASMCopyrightv2"},{"start":{"date-parts":[[2022,10,20]],"date-time":"2022-10-20T00:00:00Z","timestamp":1666224000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["NIH R01HL136706"],"award-info":[{"award-number":["NIH R01HL136706"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["1722630"],"award-info":[{"award-number":["1722630"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["R15GM104880-03"],"award-info":[{"award-number":["R15GM104880-03"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2022,10,20]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            The opportunistic human pathogen\n            <jats:named-content content-type=\"genus-species\">Pseudomonas aeruginosa<\/jats:named-content>\n            PAO1 has an extensive metabolism, enabling it to utilize a wide range of structurally diverse compounds to meet its nutritional and energy needs. Interestingly, the utilization of some of the more unusual compounds often associated with a eukaryotic-host environment is regulated via enhancer-binding proteins (EBPs) in\n            <jats:named-content content-type=\"genus-species\">P. aeruginosa<\/jats:named-content>\n            . Whether the utilization of such compounds and the EBPs involved contribute to the pathogenesis of\n            <jats:named-content content-type=\"genus-species\">P. aeruginosa<\/jats:named-content>\n            remains to be fully understood. To narrow this gap, we investigated the roles of the EBPs EatR (regulator of ethanolamine catabolism), DdaR (regulator of methylarginine catabolism), and MifR (regulator of \u03b1-ketoglutarate or \u03b1-KG transport) in the virulence of\n            <jats:named-content content-type=\"genus-species\">P. aeruginosa<\/jats:named-content>\n            PAO1 in a pneumonia-induced septic mouse model. Deletion of genes encoding EatR and DdaR had no significant effect on the mortality of\n            <jats:named-content content-type=\"genus-species\">P. aeruginosa<\/jats:named-content>\n            PAO1-infected mice compared to wide-type (WT) PAO1-infected mice. In contrast, infected mice with \u0394\n            <jats:italic>mifR<\/jats:italic>\n            mutant exhibited a significant reduction (~50%) in the mortality rate compared with WT PAO1 (\n            <jats:italic>P<\/jats:italic>\n            &lt; 0.05). Infected mice with \u0394\n            <jats:italic>mifR<\/jats:italic>\n            PAO1 had lower lung injury scores, fewer inflammatory cells, decreased proinflammatory cytokines, and decreased apoptosis and cell death compared to mice infected with WT PAO1 (\n            <jats:italic>P<\/jats:italic>\n            &lt; 0.05). Furthermore, molecular analysis revealed decreased NLRP3 inflammasome activation in infected mice with \u0394\n            <jats:italic>mifR<\/jats:italic>\n            PAO1 compared to WT PAO1 (\n            <jats:italic>P<\/jats:italic>\n            &lt; 0.05). These results suggested that the utilization of \u03b1-KG was a contributing factor in\n            <jats:named-content content-type=\"genus-species\">P. aeruginosa<\/jats:named-content>\n            -mediated pneumonia and sepsis and that MifR-associated regulation may be a potential therapeutic target for\n            <jats:named-content content-type=\"genus-species\">P. aeruginosa<\/jats:named-content>\n            infectious disease.\n          <\/jats:p>","DOI":"10.1128\/iai.00136-22","type":"journal-article","created":{"date-parts":[[2022,9,20]],"date-time":"2022-09-20T13:14:34Z","timestamp":1663679674000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":4,"title":["The Enhancer-Binding Protein MifR, an Essential Regulator of \u03b1-Ketoglutarate Transport, Is Required for Full Virulence of Pseudomonas aeruginosa PAO1 in a Mouse Model of Pneumonia"],"prefix":"10.1128","volume":"90","author":[{"given":"Weichuan","family":"Xiong","sequence":"first","affiliation":[{"name":"Department of Surgery, State University of New York (SUNY) Upstate Medical University, Syracuse, New York, USA"},{"name":"Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Perna","sequence":"additional","affiliation":[{"name":"Department of Surgery, State University of New York (SUNY) Upstate Medical University, Syracuse, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ikechukwu B.","family":"Jacob","sequence":"additional","affiliation":[{"name":"Department of Surgery, State University of New York (SUNY) Upstate Medical University, Syracuse, New York, USA"},{"name":"Department of Microbiology and Immunology, State University of New 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