{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T05:24:51Z","timestamp":1792905891630,"version":"4.5.0"},"reference-count":54,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[2018,2,1]],"date-time":"2018-02-01T00:00:00Z","timestamp":1517443200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100004793","name":"Minist\u00e8re de l'Education Nationale, de l'Enseignement Sup\u00e9rieur et de la Recherche","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004793","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2018,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Resistance of clinical strains of\n            <jats:named-content content-type=\"genus-species\">Pseudomonas aeruginosa<\/jats:named-content>\n            to aminoglycosides can result from production of transferable aminoglycoside-modifying enzymes, of 16S rRNA methylases, and\/or mutational derepression of intrinsic multidrug efflux pump MexXY(OprM). We report here the characterization of a new type of mutant that is 4- to 8-fold more resistant to 2-deoxystreptamine derivatives (e.g., gentamicin, amikacin, and tobramycin) than the wild-type strain PAO1. The genetic alterations of three\n            <jats:italic>in vitro<\/jats:italic>\n            mutants were mapped on\n            <jats:italic>fusA1<\/jats:italic>\n            and found to result in single amino acid substitutions in domains II, III, and V of elongation factor G (EF-G1A), a key component of translational machinery. Transfer of the mutated\n            <jats:italic>fusA1<\/jats:italic>\n            alleles into PAO1 reproduced the resistance phenotype. Interestingly,\n            <jats:italic>fusA1<\/jats:italic>\n            mutants with other amino acid changes in domains G, IV, and V of EF-G1A were identified among clinical strains with decreased susceptibility to aminoglycosides. Allelic-exchange experiments confirmed the relevance of these latter mutations and of three other previously reported alterations located in domains G and IV. Pump MexXY(OprM) partly contributed to the resistance conferred by the mutated EF-G1A variants and had additive effects on aminoglycoside MICs when mutationally upregulated. Altogether, our data demonstrate that cystic fibrosis (CF) and non-CF strains of\n            <jats:named-content content-type=\"genus-species\">P. aeruginosa<\/jats:named-content>\n            can acquire a therapeutically significant resistance to important aminoglycosides via a new mechanism involving mutations in elongation factor EF-G1A.\n          <\/jats:p>","DOI":"10.1128\/aac.01835-17","type":"journal-article","created":{"date-parts":[[2017,11,13]],"date-time":"2017-11-13T16:53:52Z","timestamp":1510592032000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":90,"title":["Mutations in Gene\n            <i>fusA1<\/i>\n            as a Novel Mechanism of Aminoglycoside Resistance in Clinical Strains of Pseudomonas aeruginosa"],"prefix":"10.1128","volume":"62","author":[{"given":"Arnaud","family":"Bolard","sequence":"first","affiliation":[{"name":"Centre National de R\u00e9f\u00e9rence de la R\u00e9sistance aux Antibiotiques, Laboratoire de Bact\u00e9riologie, Centre Hospitalier Universitaire Jean Minjoz, Besan\u00e7on, France"},{"name":"UMR6249 CNRS Chronoenvironnement, Universit\u00e9 de Franche-Comt\u00e9, Besan\u00e7on, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Pl\u00e9siat","sequence":"additional","affiliation":[{"name":"Centre National de R\u00e9f\u00e9rence de la R\u00e9sistance aux Antibiotiques, Laboratoire de Bact\u00e9riologie, Centre Hospitalier Universitaire Jean Minjoz, Besan\u00e7on, France"},{"name":"UMR6249 CNRS Chronoenvironnement, Universit\u00e9 de Franche-Comt\u00e9, Besan\u00e7on, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katy","family":"Jeannot","sequence":"additional","affiliation":[{"name":"Centre National de R\u00e9f\u00e9rence de la R\u00e9sistance aux Antibiotiques, Laboratoire de Bact\u00e9riologie, Centre Hospitalier Universitaire Jean Minjoz, Besan\u00e7on, France"},{"name":"UMR6249 CNRS Chronoenvironnement, Universit\u00e9 de Franche-Comt\u00e9, Besan\u00e7on, 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