{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T02:55:39Z","timestamp":1787021739234,"version":"build-2736575974"},"update-to":[{"DOI":"10.1371\/journal.pbio.3001808","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,10,10]],"date-time":"2022-10-10T00:00:00Z","timestamp":1665360000000}}],"reference-count":76,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2022,9,28]],"date-time":"2022-09-28T00:00:00Z","timestamp":1664323200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004359","name":"Vetenskapsr\u00e5det","doi-asserted-by":"publisher","award":["2017-01527"],"award-info":[{"award-number":["2017-01527"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004063","name":"Knut och Alice Wallenbergs Stiftelse","doi-asserted-by":"publisher","award":["KAW 2018.0168"],"award-info":[{"award-number":["KAW 2018.0168"]}],"id":[{"id":"10.13039\/501100004063","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosbiology.org"],"crossmark-restriction":false},"short-container-title":["PLoS Biol"],"abstract":"<jats:p>\n                    In a collection of\n                    <jats:italic>Escherichia coli<\/jats:italic>\n                    isolates, we discovered a new mechanism leading to frequent and high-level tigecycline resistance involving tandem gene amplifications of an efflux pump encoded by the\n                    <jats:italic>tet<\/jats:italic>\n                    (A) determinant. Some isolates, despite carrying a functional\n                    <jats:italic>tet<\/jats:italic>\n                    (A), could not evolve high-level tigecycline resistance by amplification due to the presence of a deletion in the TetR(A) repressor. This mutation impaired induction of\n                    <jats:italic>tetA<\/jats:italic>\n                    (A) (encoding the TetA(A) efflux pump) in presence of tetracyclines, with the strongest effect observed for tigecycline, subsequently preventing the development of\n                    <jats:italic>tet<\/jats:italic>\n                    (A) amplification-dependent high-level tigecycline resistance. We found that this mutated\n                    <jats:italic>tet<\/jats:italic>\n                    (A) determinant was common among\n                    <jats:italic>tet<\/jats:italic>\n                    (A)-carrying\n                    <jats:italic>E<\/jats:italic>\n                    .\n                    <jats:italic>coli<\/jats:italic>\n                    isolates and analysed possible explanations for this high frequency. First, while the mutated\n                    <jats:italic>tet<\/jats:italic>\n                    (A) was found in several ST-groups, we found evidence of clonal spread among ST131 isolates, which increases its frequency within\n                    <jats:italic>E<\/jats:italic>\n                    .\n                    <jats:italic>coli<\/jats:italic>\n                    databases. Second, evolution and competition experiments revealed that the mutation in\n                    <jats:italic>tetR<\/jats:italic>\n                    (A) could be positively selected over the wild-type allele at sub-inhibitory concentrations of tetracyclines. Our work demonstrates how low concentrations of tetracyclines, such as those found in contaminated environments, can enrich and select for a mutation that generates an evolutionary dead-end that precludes the evolution towards high-level, clinically relevant tigecycline resistance.\n                  <\/jats:p>","DOI":"10.1371\/journal.pbio.3001808","type":"journal-article","created":{"date-parts":[[2022,9,28]],"date-time":"2022-09-28T14:34:59Z","timestamp":1664375699000},"page":"e3001808","update-policy":"https:\/\/doi.org\/10.1371\/journal.pbio.corrections_policy","source":"Crossref","is-referenced-by-count":13,"title":["Low levels of tetracyclines select for a mutation that prevents the evolution of high-level resistance to tigecycline"],"prefix":"10.1371","volume":"20","author":[{"given":"Jennifer","family":"Jagdmann","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan 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EUCAST reading guide for broth microdilution [Internet]. 2019. 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