Investigation of the molecular evolution of carbapenem resistance in Klebsiella quasipneumoniae
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Investigation of the molecular evolution of carbapenem resistance in Klebsiella quasipneumoniae Enlace externoen Biblioteca Virtual del Banco de la República
Registro bibliográfico
- Título: Investigation of the molecular evolution of carbapenem resistance in Klebsiella quasipneumoniae
- Autor: Rosas Bastidas, Natalia Carolina
- Publicación original: 2021
- Descripción física: PDF
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Nota general:
- Colombia
- Notas de reproducción original: Digitalización realizada por la Biblioteca Virtual del Banco de la República (Colombia)
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Notas:
- Resumen: Abstract: The evolution of multidrug resistance in Klebsiella species in response to selective pressure and the extent to which this may be reversible is not fully understood. The spread of carbapenemresistant Enterobacteriaceae (CRE) is considered a public health threat by the World Health Organization (WHO) and the Centers for Disease Control and Prevention (CDC). As such, more studies are needed to understand the evolution of antibiotic resistance mechanisms to determine if it is possible to reverse this trend. Highlighted In this study, a comprehensive characterisation of a clinical Klebsiella quasipneumoniae isolate called FK688 is performed. The FK688 strain is resistant to multiple antibiotics, including third-generation cephalosporins and carbapenems and caused a bloodstream infection in a hospitalised patient. A combinational approach of genomic, enzymatic, and machine learning analyses did not uncover any carbapenemase-encoding genes in FK688. Rather, this research showed that epistatic changes are necessary for FK688 to acquire a CRE phenotype. Evolution experiments demonstrated the fitness burden associated with antimicrobial resistance determinants and the reversion to a carbapenem-susceptible phenotype in an antibiotic-free environment. Fitness assays showed that a low concentration of ceftazidime selects for a ?- lactamase gene and can potentiate evolution to carbapenem resistance by a single-step mutation in the porin OmpK36. This study demonstrated the importance of epistatic events and how variation in drug exposure can shape the evolutionary pathway to antibiotic resistance in bacteria.
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- Colfuturo
- Forma/género: tesis
- Idioma: castellano
- Institución origen: Biblioteca Virtual del Banco de la República
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Encabezamiento de materia:
- Antimicrobial resistance; Carbapenem; Membrane remodelling; Outer membrane; OmpK36; Porin; Bacterial fitness; Molecular evolution; Biological evolution; Resistencia antimicrobiana; Carbapenem; Remodelación de membranas; Proteinas de membrana externa; OmpK36, Porina, Fitness bacteriano; Evolución molecular; Evolución biológica
- Ciencias naturales y matemáticas; Ciencias naturales y matemáticas / Ciencias de la vida Biología; Tecnología; Tecnología / Ciencias médicas Medicina
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