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An integrative, multi-omics approach towards the prioritization of Klebsiella pneumoniae drug targets

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 stra...

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Autores principales: Ramos, Pablo Ivan Pereira, Fernández Do Porto, Darío, Lanzarotti, Esteban, Sosa, Ezequiel J., Burguener, Germán, Pardo, Agustín M., Klein, Cecilia C., Sagot, Marie-France, de Vasconcelos, Ana Tereza R., Gales, Ana Cristina, Marti, Marcelo, Turjanski, Adrián G., Nicolás, Marisa F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6050338/
https://www.ncbi.nlm.nih.gov/pubmed/30018343
http://dx.doi.org/10.1038/s41598-018-28916-7
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author Ramos, Pablo Ivan Pereira
Fernández Do Porto, Darío
Lanzarotti, Esteban
Sosa, Ezequiel J.
Burguener, Germán
Pardo, Agustín M.
Klein, Cecilia C.
Sagot, Marie-France
de Vasconcelos, Ana Tereza R.
Gales, Ana Cristina
Marti, Marcelo
Turjanski, Adrián G.
Nicolás, Marisa F.
author_facet Ramos, Pablo Ivan Pereira
Fernández Do Porto, Darío
Lanzarotti, Esteban
Sosa, Ezequiel J.
Burguener, Germán
Pardo, Agustín M.
Klein, Cecilia C.
Sagot, Marie-France
de Vasconcelos, Ana Tereza R.
Gales, Ana Cristina
Marti, Marcelo
Turjanski, Adrián G.
Nicolás, Marisa F.
author_sort Ramos, Pablo Ivan Pereira
collection PubMed
description 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.
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spelling pubmed-60503382018-07-19 An integrative, multi-omics approach towards the prioritization of Klebsiella pneumoniae drug targets Ramos, Pablo Ivan Pereira Fernández Do Porto, Darío Lanzarotti, Esteban Sosa, Ezequiel J. Burguener, Germán Pardo, Agustín M. Klein, Cecilia C. Sagot, Marie-France de Vasconcelos, Ana Tereza R. Gales, Ana Cristina Marti, Marcelo Turjanski, Adrián G. Nicolás, Marisa F. Sci Rep Article 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. Nature Publishing Group UK 2018-07-17 /pmc/articles/PMC6050338/ /pubmed/30018343 http://dx.doi.org/10.1038/s41598-018-28916-7 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Ramos, Pablo Ivan Pereira
Fernández Do Porto, Darío
Lanzarotti, Esteban
Sosa, Ezequiel J.
Burguener, Germán
Pardo, Agustín M.
Klein, Cecilia C.
Sagot, Marie-France
de Vasconcelos, Ana Tereza R.
Gales, Ana Cristina
Marti, Marcelo
Turjanski, Adrián G.
Nicolás, Marisa F.
An integrative, multi-omics approach towards the prioritization of Klebsiella pneumoniae drug targets
title An integrative, multi-omics approach towards the prioritization of Klebsiella pneumoniae drug targets
title_full An integrative, multi-omics approach towards the prioritization of Klebsiella pneumoniae drug targets
title_fullStr An integrative, multi-omics approach towards the prioritization of Klebsiella pneumoniae drug targets
title_full_unstemmed An integrative, multi-omics approach towards the prioritization of Klebsiella pneumoniae drug targets
title_short An integrative, multi-omics approach towards the prioritization of Klebsiella pneumoniae drug targets
title_sort integrative, multi-omics approach towards the prioritization of klebsiella pneumoniae drug targets
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6050338/
https://www.ncbi.nlm.nih.gov/pubmed/30018343
http://dx.doi.org/10.1038/s41598-018-28916-7
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