| Author | Serral, Federico | |
| Author | Pardo, Agustin M | |
| Author | Sosa, Ezequiel | |
| Author | Palomino, María Mercedes | |
| Author | Nicolás, Marisa F | |
| Author | Turjanski, Adrian G | |
| Author | Ramos, Pablo Ivan P | |
| Author | Porto, Darío Fernández do | |
| Access date | 2022-03-07T17:49:30Z | |
| Available date | 2022-03-07T17:49:30Z | |
| Document date | 2022 | |
| Citation | Serral, Federico et al. Pathway driven target selection in klebsiella pneumoniae: insights into carbapenem exposure. Frontiers in Cellular and Infection Microbiology, v. 2, p.1-14, 2022. | pt_BR |
| ISSN | 2235-2988 | pt_BR |
| URI | https://www.arca.fiocruz.br/handle/icict/51596 | |
| Sponsorship | Agencia Nacional de Promoción Científica y Tecnológica. Universidade de Buenos Aires. Conselho Nacional de Desenvolvimento Científico e Tecnológico. Coordenação de Aperfeiçoamento de Pessoal de Nível Superior. CONICET. | pt_BR |
| Language | eng | pt_BR |
| Publisher | Frontiers Media | pt_BR |
| Rights | open access | pt_BR |
| Subject in Portuguese | Klebsiella pneumoniae | pt_BR |
| Subject in Portuguese | Carbapenêmicos | pt_BR |
| Subject in Portuguese | Componentes Genômicos | pt_BR |
| Title | Pathway driven target selection in klebsiella pneumoniae: insights into carbapenem exposure | pt_BR |
| Type | Article | pt_BR |
| DOI | doi.org/10.3389/fcimb.2022.773405 | |
| Abstract | 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. | pt_BR |
| Affilliation | Universidad de Buenos Aires. Instituto de Cálculo. Facultad de Ciencias Exactas y Naturales. Buenos Aires, Argentina. | pt_BR |
| Affilliation | Universidad de Buenos Aires. Instituto de Cálculo. Facultad de Ciencias Exactas y Naturales. Buenos Aires, Argentina. | pt_BR |
| Affilliation | Universidad de Buenos Aires. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. CONICET. Buenos Aires, Argentina. | pt_BR |
| Affilliation | Universidad de Buenos Aires. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. CONICET. Buenos Aires, Argentina / Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica. Universidad de Buenos Aires. Cdad. Universitaria. Buenos Aires, Argentina. | pt_BR |
| Affilliation | Laboratório Nacional de Computação Científica. Laboratório de Bioinformática. Petrópolis, RJ, Brasil. | pt_BR |
| Affilliation | Universidad de Buenos Aires. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. CONICET. Buenos Aires, Argentina / Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica. Universidad de Buenos Aires. Cdad. Universitaria. Buenos Aires, Argentina. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Centro de Integração de Dados e Conhecimentos para a Saúde. Salvador, BA, Brasil. | pt_BR |
| Affilliation | Universidad de Buenos Aires. Instituto de Cálculo. Facultad de Ciencias Exactas y Naturales. Buenos Aires, Argentina / Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica. Universidad de Buenos Aires. Cdad. Universitaria. Buenos Aires, Argentina. | pt_BR |
| Subject | Klebsiella pneumoniae | pt_BR |
| Subject | Carbapenems | pt_BR |
| Subject | Genome Components | pt_BR |
| Subject in Spanish | Klebsiella pneumoniae | pt_BR |
| Subject in Spanish | Carbapenémicos | pt_BR |
| Subject in Spanish | Componentes Genómicos | pt_BR |
| Subject in French | Klebsiella pneumoniae | pt_BR |
| Subject in French | Carbapénèmes | pt_BR |
| Subject in French | Composants de génome | pt_BR |
