Pathway driven target selection in klebsiella pneumoniae: insights into carbapenem exposure

Detalhes bibliográficos
Autor(a) principal: Serral, Federico
Data de Publicação: 2022
Outros Autores: Pardo, Agustin M, Sosa, Ezequiel, Palomino, María Mercedes, Nicolás, Marisa F, Turjanski, Adrian G, Ramos, Pablo Ivan P, Porto, Darío Fernández do
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/51596
Resumo: 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.
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spelling Serral, FedericoPardo, Agustin MSosa, EzequielPalomino, María MercedesNicolás, Marisa FTurjanski, Adrian GRamos, Pablo Ivan PPorto, Darío Fernández do2022-03-07T17:49:30Z2022-03-07T17:49:30Z2022Serral, 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, 2022.2235-2988https://www.arca.fiocruz.br/handle/icict/51596doi.org/10.3389/fcimb.2022.773405Agencia 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.Universidad de Buenos Aires. Instituto de Cálculo. Facultad de Ciencias Exactas y Naturales. Buenos Aires, Argentina.Universidad de Buenos Aires. Instituto de Cálculo. Facultad de Ciencias Exactas y Naturales. Buenos Aires, Argentina.Universidad de Buenos Aires. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. CONICET. Buenos Aires, Argentina.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.Laboratório Nacional de Computação Científica. Laboratório de Bioinformática. Petrópolis, RJ, Brasil.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.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Centro de Integração de Dados e Conhecimentos para a Saúde. Salvador, BA, Brasil.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.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.engFrontiers MediaKlebsiella pneumoniaeCarbapenêmicosComponentes GenômicosKlebsiella pneumoniaeCarbapenemsGenome ComponentsKlebsiella pneumoniaeCarbapenémicosComponentes GenómicosKlebsiella pneumoniaeCarbapénèmesComposants de génomePathway driven target selection in klebsiella pneumoniae: insights into carbapenem exposureinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://www.arca.fiocruz.br/bitstream/icict/51596/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALSerral, F. - Pathway Driven.pdfSerral, F. - Pathway Driven.pdfapplication/pdf57468532https://www.arca.fiocruz.br/bitstream/icict/51596/2/Serral%2c%20F.%20-%20Pathway%20Driven.pdfd97f5eb3bce220cc319e83fd21d5e12eMD52icict/515962023-03-15 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dc.title.pt_BR.fl_str_mv Pathway driven target selection in klebsiella pneumoniae: insights into carbapenem exposure
title Pathway driven target selection in klebsiella pneumoniae: insights into carbapenem exposure
spellingShingle Pathway driven target selection in klebsiella pneumoniae: insights into carbapenem exposure
Serral, Federico
Klebsiella pneumoniae
Carbapenêmicos
Componentes Genômicos
Klebsiella pneumoniae
Carbapenems
Genome Components
Klebsiella pneumoniae
Carbapenémicos
Componentes Genómicos
Klebsiella pneumoniae
Carbapénèmes
Composants de génome
title_short Pathway driven target selection in klebsiella pneumoniae: insights into carbapenem exposure
title_full Pathway driven target selection in klebsiella pneumoniae: insights into carbapenem exposure
title_fullStr Pathway driven target selection in klebsiella pneumoniae: insights into carbapenem exposure
title_full_unstemmed Pathway driven target selection in klebsiella pneumoniae: insights into carbapenem exposure
title_sort Pathway driven target selection in klebsiella pneumoniae: insights into carbapenem exposure
author Serral, Federico
author_facet Serral, Federico
Pardo, Agustin M
Sosa, Ezequiel
Palomino, María Mercedes
Nicolás, Marisa F
Turjanski, Adrian G
Ramos, Pablo Ivan P
Porto, Darío Fernández do
author_role author
author2 Pardo, Agustin M
Sosa, Ezequiel
Palomino, María Mercedes
Nicolás, Marisa F
Turjanski, Adrian G
Ramos, Pablo Ivan P
Porto, Darío Fernández do
author2_role author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Serral, Federico
Pardo, Agustin M
Sosa, Ezequiel
Palomino, María Mercedes
Nicolás, Marisa F
Turjanski, Adrian G
Ramos, Pablo Ivan P
Porto, Darío Fernández do
dc.subject.other.pt_BR.fl_str_mv Klebsiella pneumoniae
Carbapenêmicos
Componentes Genômicos
topic Klebsiella pneumoniae
Carbapenêmicos
Componentes Genômicos
Klebsiella pneumoniae
Carbapenems
Genome Components
Klebsiella pneumoniae
Carbapenémicos
Componentes Genómicos
Klebsiella pneumoniae
Carbapénèmes
Composants de génome
dc.subject.en.pt_BR.fl_str_mv Klebsiella pneumoniae
Carbapenems
Genome Components
dc.subject.es.pt_BR.fl_str_mv Klebsiella pneumoniae
Carbapenémicos
Componentes Genómicos
dc.subject.fr.pt_BR.fl_str_mv Klebsiella pneumoniae
Carbapénèmes
Composants de génome
description 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.
publishDate 2022
dc.date.accessioned.fl_str_mv 2022-03-07T17:49:30Z
dc.date.available.fl_str_mv 2022-03-07T17:49:30Z
dc.date.issued.fl_str_mv 2022
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.citation.fl_str_mv 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.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/51596
dc.identifier.issn.pt_BR.fl_str_mv 2235-2988
dc.identifier.doi.none.fl_str_mv doi.org/10.3389/fcimb.2022.773405
identifier_str_mv 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.
2235-2988
doi.org/10.3389/fcimb.2022.773405
url https://www.arca.fiocruz.br/handle/icict/51596
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Frontiers Media
publisher.none.fl_str_mv Frontiers Media
dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
instname:Fundação Oswaldo Cruz (FIOCRUZ)
instacron:FIOCRUZ
instname_str Fundação Oswaldo Cruz (FIOCRUZ)
instacron_str FIOCRUZ
institution FIOCRUZ
reponame_str Repositório Institucional da FIOCRUZ (ARCA)
collection Repositório Institucional da FIOCRUZ (ARCA)
bitstream.url.fl_str_mv https://www.arca.fiocruz.br/bitstream/icict/51596/1/license.txt
https://www.arca.fiocruz.br/bitstream/icict/51596/2/Serral%2c%20F.%20-%20Pathway%20Driven.pdf
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