{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T00:44:51Z","timestamp":1778114691013,"version":"3.51.4"},"reference-count":67,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2021,3,3]],"date-time":"2021-03-03T00:00:00Z","timestamp":1614729600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"funder":[{"DOI":"10.13039\/100014067","name":"Naval Medical Research Unit and Molecular Bioeffects, Wright-Patterson Air Force Base","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100014067","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Multi-drug resistant (MDR) <jats:italic>Acinetobacter baumannii<\/jats:italic> (<jats:italic>Ab<\/jats:italic>) and <jats:italic>Acinetobacter spp<\/jats:italic>. present monumental global health challenges. These organisms represent model Gram-negative pathogens with known antibiotic resistance and biofilm-forming properties. Herein, a novel, nontoxic biocide, AB569, consisting of acidified nitrite (A-NO<jats:sub>2<\/jats:sub><jats:sup>-<\/jats:sup>) and ethylenediaminetetraacetic acid (EDTA), demonstrated bactericidal activity against all <jats:italic>Ab<\/jats:italic> and <jats:italic>Acinetobacter<\/jats:italic> spp. strains, respectively. Average <jats:underline><jats:bold>f<\/jats:bold><\/jats:underline>ractional <jats:underline><jats:bold>i<\/jats:bold><\/jats:underline>nhibitory <jats:underline><jats:bold>c<\/jats:bold><\/jats:underline>oncentrations (FICs) of 0.25 mM EDTA plus 4 mM A-NO<jats:sub>2<\/jats:sub><jats:sup>-<\/jats:sup> were observed across several clinical reference and multiple combat wound isolates from the Iraq\/Afghanistan wars. Importantly, toxicity testing on human dermal fibroblasts (HDFa) revealed an upper toxicity limit of 3 mM EDTA plus 64 mM A-NO<jats:sub>2<\/jats:sub><jats:sup>-<\/jats:sup>, and thus are in the therapeutic range for effective <jats:italic>Ab<\/jats:italic> and <jats:italic>Acinetobacter spp<\/jats:italic>. treatment. Following treatment of <jats:italic>Ab<\/jats:italic> strain ATCC 19606 with AB569, quantitative PCR analysis of selected genes products to be responsive to AB569 revealed up-regulation of iron regulated genes involved in siderophore production, siderophore biosynthesis non-ribosomal peptide synthetase module (<jats:italic>SBNRPSM<\/jats:italic>), and siderophore biosynthesis protein monooxygenase (<jats:italic>SBPM<\/jats:italic>) when compared to untreated organisms. Taken together, treating <jats:italic>Ab<\/jats:italic> infections with AB569 at inhibitory concentrations reveals the potential clinical application of preventing <jats:italic>Ab<\/jats:italic> from gaining an early growth advantage during infection followed by extensive bactericidal activity upon subsequent exposures.<\/jats:p>","DOI":"10.1371\/journal.pone.0247513","type":"journal-article","created":{"date-parts":[[2021,3,3]],"date-time":"2021-03-03T19:40:34Z","timestamp":1614800434000},"page":"e0247513","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":9,"title":["AB569, a non-toxic combination of acidified nitrite and EDTA, is effective at killing the notorious Iraq\/Afghanistan combat wound pathogens, multi-drug resistant Acinetobacter baumannii and Acinetobacter spp."],"prefix":"10.1371","volume":"16","author":[{"given":"Amy L.","family":"Bogue","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Warunya","family":"Panmanee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cameron T.","family":"McDaniel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joel E.","family":"Mortensen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edwin","family":"Kamau","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luis A.","family":"Actis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jay A.","family":"Johannigman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael J.","family":"Schurr","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Latha","family":"Satish","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0066-4563","authenticated-orcid":true,"given":"Nalinikanth","family":"Kotagiri","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2300-4955","authenticated-orcid":true,"given":"Daniel J.","family":"Hassett","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2021,3,3]]},"reference":[{"issue":"6","key":"pone.0247513.ref001","doi-asserted-by":"crossref","first-page":"1356","DOI":"10.1007\/s11999-008-0212-9","article-title":"Multidrug-resistant organisms in military wounds from Iraq and Afghanistan","volume":"466","author":"JH Calhoun","year":"2008","journal-title":"Clin Orthop Relat Res"},{"key":"pone.0247513.ref002","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1126\/science.8484121","article-title":"Clues to pathogensis of colorectal cancer","volume":"260","author":"LA Aaltonen","year":"1993","journal-title":"Science"},{"issue":"11","key":"pone.0247513.ref003","first-page":"289","article-title":"Prevention. 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