Author | Ramos, Pablo Ivan Pereira | |
Author | Fernández do Porto, Darío | |
Author | Lanzarotti, Esteban | |
Author | Sosa, Ezequiel J | |
Author | Burguener, Germán | |
Author | Pardo, Agustín M | |
Author | Klein, Cecilia C | |
Author | Sagot, Marie-France | |
Author | Vasconcelos, Ana Tereza Ribeiro de | |
Author | Gales, Ana Cristina | |
Author | Marti, Marcelo | |
Author | Turjanski, Adrián G | |
Author | Nicolás, Marisa Fabiana | |
Access date | 2018-08-24T16:20:54Z | |
Available date | 2018-08-24T16:20:54Z | |
Document date | 2018 | |
Citation | RAMOS, P. I. P. et al. An integrative, multi-omics approach towards the prioritization of Klebsiella pneumoniae drug targets. Scientific Reports, v. 8, p. 10755, 2018. | pt_BR |
ISSN | 2045-2322 | pt_BR |
URI | https://www.arca.fiocruz.br/handle/icict/28354 | |
Sponsorship | Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ/
CONICET, process no. E-26/110.315/2014) and from CNPq (process no. 307713/2016-4). ES, DFDP, AGT and MM are members of CONICET. M-FS and CCK acknowledge funding from the European Research Council under the European Community’s Seventh Framework Programme (FP7/2007-2013)/ERC grant agreement
no. [247073]10. ATRV acknowledges funding from CNPq (process 302.768/2011-4), FAPERJ (process
E-26/202.903/2015) and CAPES (process 23038.010041/2013-13). | pt_BR |
Language | eng | pt_BR |
Publisher | Nature Publishing Group | pt_BR |
Rights | open access | pt_BR |
Subject in Portuguese | Klebsiella pneumoniae | pt_BR |
Subject in Portuguese | Fatores de risco | pt_BR |
Subject in Portuguese | Infecção | pt_BR |
Subject in Portuguese | Humanos | pt_BR |
Subject in Portuguese | Resistência a antibióticos | pt_BR |
Subject in Portuguese | Patógenos | pt_BR |
Title | An integrative, multi-omics approach towards the prioritization of Klebsiella pneumoniae drug targets | pt_BR |
Type | Article | pt_BR |
DOI | 10.1038/s41598-018-28916-7 | |
Abstract | Klebsiella pneumoniae (Kp) is a globally disseminated opportunistic pathogen that can cause life-threatening infections. It has been found as the culprit of many infection outbreaks in hospital environments, being particularly aggressive towards newborns and adults under intensive care. Many Kp strains produce extended-spectrum β-lactamases, enzymes that promote resistance against antibiotics used to fight these infections. The presence of other resistance determinants leading to multidrug-resistance also limit therapeutic options, and the use of 'last-resort' drugs, such as polymyxins, is not uncommon. The global emergence and spread of resistant strains underline the need for novel antimicrobials against Kp and related bacterial pathogens. To tackle this great challenge, we generated multiple layers of 'omics' data related to Kp and prioritized proteins that could serve as attractive targets for antimicrobial development. Genomics, transcriptomics, structuromic and metabolic information were integrated in order to prioritize candidate targets, and this data compendium is freely available as a web server. Twenty-nine proteins with desirable characteristics from a drug development perspective were shortlisted, which participate in important processes such as lipid synthesis, cofactor production, and core metabolism. Collectively, our results point towards novel targets for the control of Kp and related bacterial pathogens. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Laboratório Nacional de Computação Científica. Petrópolis, RJ, Brasil | pt_BR |
Affilliation | Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Cálculo. Plataforma de Bioinformática Argentina. Buenos Aires, Argentina / Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica. Ciudad de Buenos Aires, Argentina | pt_BR |
Affilliation | Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la. Ciudad de Buenos Aires, Argentina | pt_BR |
Affilliation | Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Cálculo. Plataforma de Bioinformática Argentina. Buenos Aires, Argentina | pt_BR |
Affilliation | Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Cálculo. Plataforma de Bioinformática Argentina. Buenos Aires, Argentina | pt_BR |
Affilliation | Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la. Ciudad de Buenos Aires, Argentina | pt_BR |
Affilliation | Inria Grenoble Rhône-Alpes. Grenoble, France / Université Claude Bernard. Lyon, France / Universitat de Barcelona. Facultat de Biologia and Institut de Biomedicina. Centre for Genomic Regulation. Departament de Genètica, Microbiologia i Estadística. Barcelona, Catalonia, Spain | pt_BR |
Affilliation | Inria Grenoble Rhône-Alpes. Grenoble, France / Université Claude Bernard. Lyon, France | pt_BR |
Affilliation | Laboratório Nacional de Computação Científica. Petrópolis, RJ, Brasil | pt_BR |
Affilliation | Universidade Federal de São Paulo. Escola Paulista de Medicina. Division of Infectious Diseases. Department of Internal Medicine. Laboratório Alerta. São Paulo, SP, Brasil | pt_BR |
Affilliation | Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Cálculo. Plataforma de Bioinformática Argentina. Buenos Aires, Argentina / Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica. Ciudad de Buenos Aires, Argentina / Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la. Ciudad de Buenos Aires, Argentina | pt_BR |
Affilliation | Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Cálculo. Plataforma de Bioinformática Argentina. Buenos Aires, Argentina / Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica. Ciudad de Buenos Aires, Argentina / Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la. Ciudad de Buenos Aires, Argentina | pt_BR |
Affilliation | Laboratório Nacional de Computação Científica. Petrópolis, RJ, Brasil | pt_BR |
Subject | Klebsiella pneumoniae | pt_BR |
Subject | Risk Factors | pt_BR |
Subject | Infection | pt_BR |
Subject | Humans | pt_BR |
Subject | Antibiotic resistance | pt_BR |
Subject | Pathogens | pt_BR |