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, P.I.P., Fernández Do Porto, D., Lanzarotti, E., Sosa, E.J., Burguener, G., Pardo, A.M., Klein, C.C., Sagot, M.-F., De Vasconcelos, A.T.R., Gales, A.C., Marti, M., Turjanski, A.G., Nicolás, M.F.
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Acceso en línea:http://hdl.handle.net/20.500.12110/paper_20452322_v8_n1_p_Ramos
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spelling todo:paper_20452322_v8_n1_p_Ramos2023-10-03T16:38:27Z An integrative, multi-omics approach towards the prioritization of Klebsiella pneumoniae drug targets Ramos, P.I.P. Fernández Do Porto, D. Lanzarotti, E. Sosa, E.J. Burguener, G. Pardo, A.M. Klein, C.C. Sagot, M.-F. De Vasconcelos, A.T.R. Gales, A.C. Marti, M. Turjanski, A.G. Nicolás, M.F. 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. © 2018 The Author(s). JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_20452322_v8_n1_p_Ramos
institution Universidad de Buenos Aires
institution_str I-28
repository_str R-134
collection Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
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. © 2018 The Author(s).
format JOUR
author Ramos, P.I.P.
Fernández Do Porto, D.
Lanzarotti, E.
Sosa, E.J.
Burguener, G.
Pardo, A.M.
Klein, C.C.
Sagot, M.-F.
De Vasconcelos, A.T.R.
Gales, A.C.
Marti, M.
Turjanski, A.G.
Nicolás, M.F.
spellingShingle Ramos, P.I.P.
Fernández Do Porto, D.
Lanzarotti, E.
Sosa, E.J.
Burguener, G.
Pardo, A.M.
Klein, C.C.
Sagot, M.-F.
De Vasconcelos, A.T.R.
Gales, A.C.
Marti, M.
Turjanski, A.G.
Nicolás, M.F.
An integrative, multi-omics approach towards the prioritization of Klebsiella pneumoniae drug targets
author_facet Ramos, P.I.P.
Fernández Do Porto, D.
Lanzarotti, E.
Sosa, E.J.
Burguener, G.
Pardo, A.M.
Klein, C.C.
Sagot, M.-F.
De Vasconcelos, A.T.R.
Gales, A.C.
Marti, M.
Turjanski, A.G.
Nicolás, M.F.
author_sort Ramos, P.I.P.
title 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_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_sort integrative, multi-omics approach towards the prioritization of klebsiella pneumoniae drug targets
url http://hdl.handle.net/20.500.12110/paper_20452322_v8_n1_p_Ramos
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