Caracterización de KPC-24 y análisis de su capacidad de transferencia desde Klebsiella pneumoniae a otros bacilos Gram negativos.
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Date
2026
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Publisher
Universidad de Concepción
Abstract
La emergencia y diseminación de variantes de Klebsiella pneumoniae carbapenemasa (KPC) representan un desafío creciente para el diagnóstico y tratamiento de infecciones por bacilos Gram negativos resistentes a carbapenémicos. En Chile, KPC-2 constituye la variante predominante, sin embargo, se han descrito variantes menos frecuentes cuyo impacto funcional y epidemiológico se encuentra poco caracterizado. Entre éstas, KPC-24, descrita por primera vez en Chile, corresponde a una variante derivada de KPC-2 cuya actividad enzimática no ha sido estudiada previamente. En este estudio, se determinó la actividad enzimática de KPC-24 y se analizó la capacidad de transferencia del gen blaKPC-24 desde un aislado clínico de K. pneumoniae (UC331) hacia otros bacilos Gram negativos. Los resultados indican que KPC-24 presenta una actividad hidrolítica frente a carbapenémicos comparable a KPC-2, esto, debido a que la sustitución R6P se ubica en el péptido señal, sin afectar la estructura terciaria de la enzima. Los ensayos de conjugación no permitieron demostrar la transferencia del gen en las condiciones evaluadas, sin embargo, el análisis del ambiente genético de blaKPC-24, reveló una alta identidad con la plataforma genética NTE_KPC-1a, caracterizada por la conservación del bloque genético ISKpn6-korC-klcA-repA, previamente asociado a la diseminación de blaKPC en distintos países. En conjunto, estos hallazgos confirman que KPC-24 corresponde a una variante funcional dentro del linaje de KPC-2 y se destaca la relevancia de elementos no-Tn4401 en la diseminación de blaKPC. Asimismo, los resultados subrayan la necesidad de considerar la diversidad genética de KPC en el diseño de estrategias diagnósticas y de vigilancia epidemiológica.
The emergence and dissemination of Klebsiella pneumoniae carbapenemase (KPC) variants represent a growing challenge for the diagnosis and treatment of carbapenem-resistant Gram-negative infections. In Chile, KPC-2 is the predominant variant; however, less frequent variants have been reported whose functional and epidemiological impact remains poorly characterized. Among these, KPC-24, first described in Chile, is a KPC-2-derived whose enzymatic activity had not been previously investigated. In this study, the enzymatic activity of KPC-24 was characterized, and the transferability of the blaKPC-24 gene from a clinical K. pneumoniae isolate (UC331) to other Gram-negative bacilli was evaluated. The results indicate that KPC-24 (R6P) exhibits carbapenem-hydrolyzing activity comparable to that of KPC-2, which is consistent with the localization of the substitution within the signal peptide and its lack of impact on the structure of the mature enzyme. Conjugation assays did not demonstrate gene transfer under the conditions tested; however, analysis of the genetic environment of blaKPC-24 revealed a high degree of similarity to the NTE_KPC-1a genetic platform, characterized by conservation of the ISKpn6–korC–klcA–repA gene cluster, previously associated with the dissemination of blaKPC in different countries. Overall, these findings confirm that KPC-24 represents a functional variant within the KPC-2 lineage and highlight the relevance of non-Tn4401 elements in the dissemination of blaKPC. In addition, the results emphasize the importance of considering KPC genetic diversity in the design of diagnostic strategies and epidemiological surveillance.
The emergence and dissemination of Klebsiella pneumoniae carbapenemase (KPC) variants represent a growing challenge for the diagnosis and treatment of carbapenem-resistant Gram-negative infections. In Chile, KPC-2 is the predominant variant; however, less frequent variants have been reported whose functional and epidemiological impact remains poorly characterized. Among these, KPC-24, first described in Chile, is a KPC-2-derived whose enzymatic activity had not been previously investigated. In this study, the enzymatic activity of KPC-24 was characterized, and the transferability of the blaKPC-24 gene from a clinical K. pneumoniae isolate (UC331) to other Gram-negative bacilli was evaluated. The results indicate that KPC-24 (R6P) exhibits carbapenem-hydrolyzing activity comparable to that of KPC-2, which is consistent with the localization of the substitution within the signal peptide and its lack of impact on the structure of the mature enzyme. Conjugation assays did not demonstrate gene transfer under the conditions tested; however, analysis of the genetic environment of blaKPC-24 revealed a high degree of similarity to the NTE_KPC-1a genetic platform, characterized by conservation of the ISKpn6–korC–klcA–repA gene cluster, previously associated with the dissemination of blaKPC in different countries. Overall, these findings confirm that KPC-24 represents a functional variant within the KPC-2 lineage and highlight the relevance of non-Tn4401 elements in the dissemination of blaKPC. In addition, the results emphasize the importance of considering KPC genetic diversity in the design of diagnostic strategies and epidemiological surveillance.
Description
Tesis presentada para optar al grado de Magíster en Ciencias con mención Microbiología.
Keywords
Infección hospitalaria, Bacilos, Microbiología