The polymyxin B-induced transcriptomic response of a clinical, multidrug-resistant Klebsiella pneumoniae involves multiple regulatory elements and intracellular targets

Background: The emergence of multidrug-resistant Klebsiella pneumoniae is a major public health concern. Many K. pneumoniae infections can only be treated when resorting to last-line drugs such as polymyxin B (PB). However, resistance to this antibiotic is also observed, although insufficient infor...

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Autores principales: Pereira Ramos, Pablo Iván, Flores Custódio, Márlon Grégori, Quispe Saji, Guadalupe del Rosario, Cardoso, Thiago, Lucchetti da Silva, Gisele, Braun, Graziela, Martins, Willames M.B.S., Girardello, Raquel, Ribeiro de Vasconcelos1, Ana Tereza, Fernández, Elmer Andrés, Gales, Ana Cristina, Nicolás, Marisa Fabiana
Formato: Artículo acceptedVersion
Lenguaje:Español
Publicado: BioMed Central Ltd 2016
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Acceso en línea:http://pa.bibdigital.ucc.edu.ar/4229/1/A_PereiraRamos.pdf
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id I38-R144-4229
record_format dspace
institution Universidad Católica de Córdoba
institution_str I-38
repository_str R-144
collection Producción Académica Universidad Católica de Córdoba (UCCor)
language Español
orig_language_str_mv spa
topic Q Ciencia (General)
TA Ingeniería de asistencia técnica (General). Ingeniería Civil (General)
spellingShingle Q Ciencia (General)
TA Ingeniería de asistencia técnica (General). Ingeniería Civil (General)
Pereira Ramos, Pablo Iván
Flores Custódio, Márlon Grégori
Quispe Saji, Guadalupe del Rosario
Cardoso, Thiago
Lucchetti da Silva, Gisele
Braun, Graziela
Martins, Willames M.B.S.
Girardello, Raquel
Ribeiro de Vasconcelos1, Ana Tereza
Fernández, Elmer Andrés
Gales, Ana Cristina
Nicolás, Marisa Fabiana
The polymyxin B-induced transcriptomic response of a clinical, multidrug-resistant Klebsiella pneumoniae involves multiple regulatory elements and intracellular targets
topic_facet Q Ciencia (General)
TA Ingeniería de asistencia técnica (General). Ingeniería Civil (General)
description Background: The emergence of multidrug-resistant Klebsiella pneumoniae is a major public health concern. Many K. pneumoniae infections can only be treated when resorting to last-line drugs such as polymyxin B (PB). However, resistance to this antibiotic is also observed, although insufficient information is described on its mode of action as well as the mechanisms used by resistant bacteria to evade its effects. We aimed to study PB resistance and the influence of abiotic stresses in a clinical K. pneumoniae strain using whole transcriptome profiling. Results: We sequenced 12 cDNA libraries of K. pneumoniae Kp13 bacteria, from two biological replicates of the original strain Kp13 (Kp13) and five derivative strains: induced high-level PB resistance in acidic pH (Kp13pH), magnesium deprivation (Kp13Mg), high concentrations of calcium (Kp13Ca) and iron (Kp13Fe), and a control condition with PB (Kp13PolB). Our results show the involvement of multiple regulatory loci that differentially respond to each condition as well as a shared gene expression response elicited by PB treatment, and indicate the participation of two-regulatory components such as ArcA-ArcB, which could be involved in re-routing the K. pneumoniae metabolism following PB treatment. Modules of co-expressed genes could be determined, which correlated to growth in acid stress and PB exposure. We hypothesize that polymyxin B induces metabolic shifts in K. pneumoniae that could relate to surviving against the action of this antibiotic. Conclusions: We obtained whole transcriptome data for K. pneumoniae under different environmental conditions and PB treatment. Our results supports the notion that the K. pneumoniae response to PB exposure goes beyond damaged membrane reconstruction and involves recruitment of multiple gene modules and intracellular targets.
format Artículo
Artículo
acceptedVersion
author Pereira Ramos, Pablo Iván
Flores Custódio, Márlon Grégori
Quispe Saji, Guadalupe del Rosario
Cardoso, Thiago
Lucchetti da Silva, Gisele
Braun, Graziela
Martins, Willames M.B.S.
Girardello, Raquel
Ribeiro de Vasconcelos1, Ana Tereza
Fernández, Elmer Andrés
Gales, Ana Cristina
Nicolás, Marisa Fabiana
author_facet Pereira Ramos, Pablo Iván
Flores Custódio, Márlon Grégori
Quispe Saji, Guadalupe del Rosario
Cardoso, Thiago
Lucchetti da Silva, Gisele
Braun, Graziela
Martins, Willames M.B.S.
Girardello, Raquel
Ribeiro de Vasconcelos1, Ana Tereza
Fernández, Elmer Andrés
Gales, Ana Cristina
Nicolás, Marisa Fabiana
author_sort Pereira Ramos, Pablo Iván
title The polymyxin B-induced transcriptomic response of a clinical, multidrug-resistant Klebsiella pneumoniae involves multiple regulatory elements and intracellular targets
title_short The polymyxin B-induced transcriptomic response of a clinical, multidrug-resistant Klebsiella pneumoniae involves multiple regulatory elements and intracellular targets
title_full The polymyxin B-induced transcriptomic response of a clinical, multidrug-resistant Klebsiella pneumoniae involves multiple regulatory elements and intracellular targets
title_fullStr The polymyxin B-induced transcriptomic response of a clinical, multidrug-resistant Klebsiella pneumoniae involves multiple regulatory elements and intracellular targets
title_full_unstemmed The polymyxin B-induced transcriptomic response of a clinical, multidrug-resistant Klebsiella pneumoniae involves multiple regulatory elements and intracellular targets
title_sort polymyxin b-induced transcriptomic response of a clinical, multidrug-resistant klebsiella pneumoniae involves multiple regulatory elements and intracellular targets
publisher BioMed Central Ltd
publishDate 2016
url http://pa.bibdigital.ucc.edu.ar/4229/1/A_PereiraRamos.pdf
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spelling I38-R144-42292024-03-19T14:32:54Z http://pa.bibdigital.ucc.edu.ar/4229/ The polymyxin B-induced transcriptomic response of a clinical, multidrug-resistant Klebsiella pneumoniae involves multiple regulatory elements and intracellular targets Pereira Ramos, Pablo Iván Flores Custódio, Márlon Grégori Quispe Saji, Guadalupe del Rosario Cardoso, Thiago Lucchetti da Silva, Gisele Braun, Graziela Martins, Willames M.B.S. Girardello, Raquel Ribeiro de Vasconcelos1, Ana Tereza Fernández, Elmer Andrés Gales, Ana Cristina Nicolás, Marisa Fabiana Q Ciencia (General) TA Ingeniería de asistencia técnica (General). Ingeniería Civil (General) Background: The emergence of multidrug-resistant Klebsiella pneumoniae is a major public health concern. Many K. pneumoniae infections can only be treated when resorting to last-line drugs such as polymyxin B (PB). However, resistance to this antibiotic is also observed, although insufficient information is described on its mode of action as well as the mechanisms used by resistant bacteria to evade its effects. We aimed to study PB resistance and the influence of abiotic stresses in a clinical K. pneumoniae strain using whole transcriptome profiling. Results: We sequenced 12 cDNA libraries of K. pneumoniae Kp13 bacteria, from two biological replicates of the original strain Kp13 (Kp13) and five derivative strains: induced high-level PB resistance in acidic pH (Kp13pH), magnesium deprivation (Kp13Mg), high concentrations of calcium (Kp13Ca) and iron (Kp13Fe), and a control condition with PB (Kp13PolB). Our results show the involvement of multiple regulatory loci that differentially respond to each condition as well as a shared gene expression response elicited by PB treatment, and indicate the participation of two-regulatory components such as ArcA-ArcB, which could be involved in re-routing the K. pneumoniae metabolism following PB treatment. Modules of co-expressed genes could be determined, which correlated to growth in acid stress and PB exposure. We hypothesize that polymyxin B induces metabolic shifts in K. pneumoniae that could relate to surviving against the action of this antibiotic. Conclusions: We obtained whole transcriptome data for K. pneumoniae under different environmental conditions and PB treatment. Our results supports the notion that the K. pneumoniae response to PB exposure goes beyond damaged membrane reconstruction and involves recruitment of multiple gene modules and intracellular targets. BioMed Central Ltd 2016-12-31 application/pdf spa http://pa.bibdigital.ucc.edu.ar/4229/1/A_PereiraRamos.pdf Pereira Ramos, Pablo Iván, Flores Custódio, Márlon Grégori, Quispe Saji, Guadalupe del Rosario, Cardoso, Thiago, Lucchetti da Silva, Gisele, Braun, Graziela, Martins, Willames M.B.S., Girardello, Raquel, Ribeiro de Vasconcelos1, Ana Tereza, Fernández, Elmer Andrés ORCID: https://orcid.org/0000-0002-4711-8634 <https://orcid.org/0000-0002-4711-8634>, Gales, Ana Cristina and Nicolás, Marisa Fabiana (2016) The polymyxin B-induced transcriptomic response of a clinical, multidrug-resistant Klebsiella pneumoniae involves multiple regulatory elements and intracellular targets. BMC Genomics, 17 (S8). pp. 447-462. ISSN 1471-2164 info:eu-repo/semantics/altIdentifier/doi/https://doi.org/10.1186/s12864-016-3070-y info:eu-repo/semantics/article info:ar-repo/semantics/artículo info:eu-repo/semantics/acceptedVersion Fil: Pereira Ramos, Pablo Iván. Laboratório Nacional de Computação Científica; Brasil Fil: Flores Custódio, Márlon Grégori. Laboratório Nacional de Computação Científica; Brasil Fil: Quispe Saji, Guadalupe del Rosario. Laboratório Nacional de Computação Científica; Brasil Fil: Cardoso, Thiago. Laboratório Nacional de Computação Científica; Brasil Fil: Lucchetti da Silva, Gisele. Laboratório Nacional de Computação Científica; Brasil Fil: Braun, Graziela. Laboratório Alerta. Division of Infectious Diseases, Department of Internal Medicine, Escola Paulista de Medicina/Universidade Federal de São Paulo; Brasil Fil: Martins, Willames M.B.S. Laboratório Alerta. Division of Infectious Diseases, Department of Internal Medicine, Escola Paulista de Medicina/Universidade Federal de São Paulo; Brasil Fil: Girardello, Raquel. Laboratório Alerta. Division of Infectious Diseases, Department of Internal Medicine, Escola Paulista de Medicina/Universidade Federal de São Paulo; Brasil Fil: Ribeiro de Vasconcelos, Ana Tereza. Laboratório Nacional de Computação Científica; Brasil Fil: Fernández, Elmer Andrés. Universidad Católica de Córdoba. Facultad de Ingeniería; Argentina Fil: Gales, Ana Cristina. Laboratório Alerta. Division of Infectious Diseases, Department of Internal Medicine, Escola Paulista de Medicina/Universidade Federal de São Paulo; Brasil Fil: Nicolás, Marisa Fabiana. Laboratório Nacional de Computação Científica; Brasil info:eu-repo/semantics/openAccess https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es