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The evolutionary mechanism of non-carbapenemase carbapenem-resistant phenotypes in Klebsiella spp

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Año de publicación 2023
Idioma Inglés
Publicado por eLife

Descripción: Abstract: Antibiotic resistance is driven by selection, but the degree to which a bacterial strain’s evolutionary history shapes the mechanism and strength of resistance remains an open question. Here, we reconstruct the genetic and evolutionary mechanisms of carbapenem resistance in a clinical isolate of Klebsiella quasipneumoniae. A combination of short- and long-read sequencing, machine learning, and genetic and enzymatic analyses established that this carbapenem-resistant strain carries no carbapenemase-encoding genes. Genetic reconstruction of the resistance phenotype confirmed that two distinct genetic loci are necessary in order for the strain to acquire carbapenem resistance. Experimental evolution of the carbapenem-resistant strains in growth conditions without the antibiotic revealed that both loci confer a significant cost and are readily lost by de novo mutations resulting in the rapid evolution of a carbapenem-sensitive phenotype. To explain how carbapenem resistance evolves via multiple, low-fitness single-locus intermediates, we hypothesised that one of these loci had previously conferred adaptation to another antibiotic. Fitness assays in a range of drug concentrations show how selection in the antibiotic ceftazidime can select for one gene (blaDHA-1) potentiating the evolution of carbapenem resistance by a single mutation in a second gene (ompK36). These results show how a patient’s treatment history might shape the evolution of antibiotic resistance and could explain the genetic basis of carbapenem-resistance found in many enteric-pathogens.
Citación recomendada (normas APA)
: Natalia Carolina; Wilksch Rosas Bastidas, "The evolutionary mechanism of non-carbapenemase carbapenem-resistant phenotypes in Klebsiella spp", Colombia:eLife, 2023. Consultado en línea en la Biblioteca Digital de Bogotá (https://www.bibliotecadigitaldebogota.gov.co/resources/3711973/), el día 2025-11-21.

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- Medicina
Derechos de uso Derechos reservados
Fuente Biblioteca Virtual Banco de la República
Términos y condiciones de uso Más información aquí
Año de publicación 2023
Formato PDF
Cobertura Colombia

The evolutionary mechanism of non-carbapenemase carbapenem-resistant phenotypes in Klebsiella spp

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The evolutionary mechanism of non-carbapenemase carbapenem-resistant phenotypes in Klebsiella spp

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