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Artículo

Pathway Driven Target Selection in Klebsiella pneumoniae: Insights Into Carbapenem Exposure

Serral, FedericoIcon ; Pardo, Agustin MariaIcon ; Sosa, EzequielIcon ; Palomino, Maria MercedesIcon ; Nicolás, Marisa F.; Turjanski, AdrianIcon ; Ramos, Pablo Ivan P.; Fernández Do Porto, Darío AugustoIcon
Fecha de publicación: 01/2022
Editorial: Frontiers Media
Revista: Frontiers in Cellular and Infection Microbiology
e-ISSN: 2235-2988
Idioma: Inglés
Tipo de recurso: Artículo publicado
Clasificación temática:
Biofísica

Resumen

Carbapenem-resistant Klebsiella pneumoniae (CR-KP) represents an emerging threat to public health. CR-KP infections result in elevated morbidity and mortality. This fact, coupled with their global dissemination and increasingly limited number of therapeutic options, highlights the urgency of novel antimicrobials. Innovative strategies linking genome-wide interrogation with multi-layered metabolic data integration can accelerate the early steps of drug development, particularly target selection. Using the BioCyc ontology, we generated and manually refined a metabolic network for a CR-KP, K. pneumoniae Kp13. Converted into a reaction graph, we conducted topological-based analyses in this network to prioritize pathways exhibiting druggable features and fragile metabolic points likely exploitable to develop novel antimicrobials. Our results point to the aptness of previously recognized pathways, such as lipopolysaccharide and peptidoglycan synthesis, and casts light on the possibility of targeting less explored cellular functions. These functions include the production of lipoate, trehalose, glycine betaine, and flavin, as well as the salvaging of methionine. Energy metabolism pathways emerged as attractive targets in the context of carbapenem exposure, targeted either alone or in conjunction with current therapeutic options. These results prompt further experimental investigation aimed at controlling this highly relevant pathogen.
Palabras clave: CARBAPENEM RESISTANCE , DRUG TARGETING , GENOME-SCALE METABOLIC MODELS , KLEBSIELLA PNEUMONIAE , TARGET SELECTION
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info:eu-repo/semantics/openAccess Excepto donde se diga explícitamente, este item se publica bajo la siguiente descripción: Creative Commons Attribution 2.5 Unported (CC BY 2.5)
Identificadores
URI: http://hdl.handle.net/11336/213488
URL: https://www.frontiersin.org/articles/10.3389/fcimb.2022.773405/full
DOI: https://doi.org/10.3389/fcimb.2022.773405
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Articulos(IQUIBICEN)
Articulos de INSTITUTO DE QUIMICA BIOLOGICA DE LA FACULTAD DE CS. EXACTAS Y NATURALES
Citación
Serral, Federico; Pardo, Agustin Maria; Sosa, Ezequiel; Palomino, Maria Mercedes; Nicolás, Marisa F.; et al.; Pathway Driven Target Selection in Klebsiella pneumoniae: Insights Into Carbapenem Exposure; Frontiers Media; Frontiers in Cellular and Infection Microbiology; 12; 1-2022; 1-14
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