{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T07:14:19Z","timestamp":1780470859298,"version":"3.54.1"},"reference-count":46,"publisher":"American Society for Microbiology","issue":"11","license":[{"start":{"date-parts":[[2024,11,6]],"date-time":"2024-11-06T00:00:00Z","timestamp":1730851200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/doi.org\/10.1128\/ASMCopyrightv2"},{"start":{"date-parts":[[2024,11,6]],"date-time":"2024-11-06T00:00:00Z","timestamp":1730851200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"crossref","award":["ESAAM"],"award-info":[{"award-number":["ESAAM"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2024,11,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>\n              The fitness cost associated with antimicrobial resistance has an important influence on evolutionary dynamics. We compared the genomes of three\n              <jats:italic>Klebsiella aerogenes<\/jats:italic>\n              isolates recovered from blood samples or deep abscess cultures from the same patient: the wild-type strain (CT_WT), a piperacillin-tazobactam-resistant strain (CT_PENI), and an extended-spectrum-cephalosporin (ESC)-resistant strain (CT_R). Whole-genome sequencing revealed that CT_PENI had acquired a TEM-1 \u03b2-lactamase with a mutated promoter, accounting for overproduction. CT_PENI then acquired an E240G substitution in the TEM-1 \u03b2-lactamase (resulting in TEM-207) and lost the porin-encoding\n              <jats:italic>ompK36<\/jats:italic>\n              gene to give CT_R. All three strains showed the same virulence in a mouse model of intraperitoneal infection. The results of recombination and transformation assays indicated that when present separately, the TEM-207 overproduction and the\n              <jats:italic>ompK36<\/jats:italic>\n              gene deletion had only small effects on susceptibility to ESCs. However, the combination of the two changes led to a much lower susceptibility to ESCs. Moreover, the levels of fitness\n              <jats:italic>in vitro<\/jats:italic>\n              and\n              <jats:italic>in vivo<\/jats:italic>\n              in a murine model of gut colonization were significantly lower after TEM-1 \u03b2-lactamase overproduction and lower still after E240G substitution and OmpK36 loss. We hypothesize that the chosen courses of antibiotics led to the stepwise emergence of a clone with resistance to penicillins and ESCs and no loss of virulence. However, acquired resistance may have a fitness cost that limits evolutionary success. Our results might explain why the overproduction of extended-spectrum \u03b2-lactamases (which should confer a high level of piperacillin-tazobactam resistance) is not observed in clinical practice and why TEM-207 has rarely been detected in clinical isolates.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/aac.01036-24","type":"journal-article","created":{"date-parts":[[2024,9,24]],"date-time":"2024-09-24T13:06:53Z","timestamp":1727183213000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":2,"title":["Molecular insights into the evolutionary trajectory of a\n            <i>Klebsiella aerogenes<\/i>\n            clinical isolate with a complex trade-off between resistance and virulence"],"prefix":"10.1128","volume":"68","author":[{"given":"Youssouf","family":"Sereme","sequence":"first","affiliation":[{"name":"CNRS, INSERM, Institut Necker Enfants Malades, Universit\u00e9 Paris Cit\u00e9, Paris, 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