{"id":7706,"date":"2024-09-24T12:12:46","date_gmt":"2024-09-24T10:12:46","guid":{"rendered":"https:\/\/fhu-premimpact.org\/?post_type=publication&#038;p=7706"},"modified":"2024-11-25T12:22:58","modified_gmt":"2024-11-25T11:22:58","slug":"molecular-insights-into-the-evolutionary-trajectory-of-a-klebsiella-aerogenes-clinical-isolate-with-a-complex-trade-off-between-resistance-and-virulence","status":"publish","type":"publication","link":"https:\/\/fhu-premimpact.org\/en\/publications\/molecular-insights-into-the-evolutionary-trajectory-of-a-klebsiella-aerogenes-clinical-isolate-with-a-complex-trade-off-between-resistance-and-virulence\/","title":{"rendered":"Molecular insights into the evolutionary trajectory of a Klebsiella aerogenes clinical isolate with a complex trade-off between resistance and virulence"},"content":{"rendered":"\n<h4 class=\"wp-block-heading\">Abstract<\/h4>\n\n\n\n<p>The fitness cost associated with antimicrobial resistance has an important influence on evolutionary dynamics. We compared the genomes of three <em>Klebsiella aerogenes<\/em> 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 <em>ompK36<\/em> 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 <em>ompK36<\/em> 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 <em>in vitro<\/em> and <em>in vivo<\/em> 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.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Antimicrob Agents Chemother. 2024 Nov 6;68(11):e0103624. <\/p>\n","protected":false},"featured_media":0,"template":"","class_list":["post-7706","publication","type-publication","status-publish","hentry"],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.2 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Molecular insights into the evolutionary trajectory of a Klebsiella aerogenes clinical isolate with a complex trade-off between resistance and virulence - FHU Prem&#039;IMPACT<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/fhu-premimpact.org\/en\/publications\/molecular-insights-into-the-evolutionary-trajectory-of-a-klebsiella-aerogenes-clinical-isolate-with-a-complex-trade-off-between-resistance-and-virulence\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Molecular insights into the evolutionary trajectory of a Klebsiella aerogenes clinical isolate with a complex trade-off between resistance and virulence - 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