{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T13:10:03Z","timestamp":1791897003428,"version":"4.3.4"},"reference-count":36,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2024,10,3]],"date-time":"2024-10-03T00:00:00Z","timestamp":1727913600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,10,3]],"date-time":"2024-10-03T00:00:00Z","timestamp":1727913600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"HHS | National Institutes of Health","award":["SC3GM125556"],"award-info":[{"award-number":["SC3GM125556"]}]},{"name":"HHS | National Institutes of Health","award":["R01AI100560, R01AI072219, R01AI063517"],"award-info":[{"award-number":["R01AI100560, R01AI072219, R01AI063517"]}]},{"name":"HHS | National Institutes of Health","award":["2R15 AI047115"],"award-info":[{"award-number":["2R15 AI047115"]}]},{"name":"Cleveland Department of Veterans Affairs","award":["1I01BX001974"],"award-info":[{"award-number":["1I01BX001974"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Microbiol Spectr"],"published-print":{"date-parts":[[2024,10,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>\n              Cefiderocol, a siderophore-cephalosporine conjugate antibiotic, shows promise as a therapeutic option for carbapenem-resistant (CR)\n              <jats:italic>Acinetobacter<\/jats:italic>\n              infections. While resistance has already been reported in\n              <jats:italic>A. baumannii<\/jats:italic>\n              , combination therapies with avibactam or sulbactam reduce MICs of cefiderocol, extending its efficacy. However, careful consideration is necessary when using these combinations. In our experiments, exposure of\n              <jats:italic>A. baumannii<\/jats:italic>\n              and\n              <jats:italic>A. lwoffii<\/jats:italic>\n              to cefiderocol and sulbactam or avibactam led to the selection of cefiderocol-resistant strains. Three of those were subjected to whole genome sequencing and transcriptomic analysis. The strains all possessed synonymous and non-synonymous substitutions and short deletions. The most significant mutations affected efflux pumps, transcriptional regulators, and iron homeostasis genes. Transcriptomics showed significant alterations in expression levels of outer membrane proteins, iron homeostasis, and \u03b2-lactamases, suggesting adaptive responses to selective pressure. This study underscores the importance of carefully assessing drug synergies, as they may inadvertently foster the selection of resistant variants and complicate the management of CR\n              <jats:italic>Acinetobacter<\/jats:italic>\n              infections.\n            <\/jats:p>\n            <jats:sec>\n              <jats:title>IMPORTANCE<\/jats:title>\n              <jats:p>\n                The emergence of carbapenem-resistant\n                <jats:italic>Acinetobacter<\/jats:italic>\n                strains as a serious global health threat underscores the urgent need for effective treatment options. Although few drugs show promise against CR\n                <jats:italic>Acinetobacter<\/jats:italic>\n                infections, resistance to both drugs has been reported. In this study, the molecular characterization of spontaneous cefiderocol-resistant variants, a CR\n                <jats:italic>A. baumannii<\/jats:italic>\n                strain with antagonism to sulbactam, and an\n                <jats:italic>A. lwoffii<\/jats:italic>\n                strain with antagonism to avibactam, provides valuable insights into the mechanisms of resistance to cefiderocol. Some mechanisms observed are associated with mutations affecting efflux pumps, regulators, and iron homeostasis genes. These findings highlight the importance of understanding resistance mechanisms to optimize treatment options. They also emphasize the importance of early evaluation of drug synergies to address the challenges of antimicrobial resistance in\n                <jats:italic>Acinetobacter<\/jats:italic>\n                infections.\n              <\/jats:p>\n            <\/jats:sec>\n          <\/jats:sec>","DOI":"10.1128\/spectrum.00930-24","type":"journal-article","created":{"date-parts":[[2024,8,20]],"date-time":"2024-08-20T13:05:01Z","timestamp":1724159101000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":3,"title":["Hetero-antagonism of avibactam and sulbactam with cefiderocol in carbapenem-resistant\n            <i>Acinetobacter<\/i>\n            spp."],"prefix":"10.1128","volume":"12","author":[{"given":"Olivia","family":"Wong","sequence":"first","affiliation":[{"name":"Center for Applied Biotechnology Studies, Department of Biological Science, College of Natural Sciences and Mathematics, California State University Fullerton, Fullerton, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vyanka","family":"Mezcord","sequence":"additional","affiliation":[{"name":"Center for Applied Biotechnology Studies, Department of Biological Science, College of Natural Sciences and Mathematics, California State University Fullerton, Fullerton, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Lopez","sequence":"additional","affiliation":[{"name":"Center for Applied Biotechnology Studies, Department of Biological Science, College of Natural Sciences and Mathematics, California State University Fullerton, Fullerton, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4780-5311","authenticated-orcid":false,"given":"German Matias","family":"Traglia","sequence":"additional","affiliation":[{"name":"Unidad de Gen\u00f3mica y Bioinform\u00e1tica, Departamento de Ciencias Biol\u00f3gicas, CENUR Litoral Norte, Universidad de la Rep\u00fablica, Salto, Uruguay"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5840-5869","authenticated-orcid":false,"given":"Fernando","family":"Pasteran","sequence":"additional","affiliation":[{"name":"Laboratorio Nacional\/Regional de Referencia en Antimicrobianos, Instituto Nacional de Enfermedades Infecciosas, ANLIS Dr. Carlos G. Malbr\u00e1n, Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0234-4643","authenticated-orcid":false,"given":"Marisel R.","family":"Tuttobene","sequence":"additional","affiliation":[{"name":"\u00c1rea Biolog\u00eda Molecular, Facultad de Ciencias Bioqu\u00edmicas y Farmac\u00e9uticas, Universidad Nacional de Rosario, Rosario, Argentina"},{"name":"Instituto de Biolog\u00eda Molecular y Celular de Rosario (IBR, CONICET-UNR), Rosario, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandra","family":"Corso","sequence":"additional","affiliation":[{"name":"Laboratorio Nacional\/Regional de Referencia en Antimicrobianos, Instituto Nacional de Enfermedades Infecciosas, ANLIS Dr. Carlos G. 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