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Proteomic Analysis of Drug-Resistant Mycobacteria: Co-Evolution of Copper and INH Resistance
Tuberculosis, caused by the pathogen Mycobacterium tuberculosis, is a worldwide public health threat. Mycobacterium tuberculosis is capable of resisting various stresses in host cells, including high levels of ROS and copper ions. To better understand the resistance mechanisms of mycobacteria to cop...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2015
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4452738/ https://www.ncbi.nlm.nih.gov/pubmed/26035302 http://dx.doi.org/10.1371/journal.pone.0127788 |
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author | Chen, Yuling Yang, Fan Sun, Zhongyuan Wang, Qingtao Mi, Kaixia Deng, Haiteng |
author_facet | Chen, Yuling Yang, Fan Sun, Zhongyuan Wang, Qingtao Mi, Kaixia Deng, Haiteng |
author_sort | Chen, Yuling |
collection | PubMed |
description | Tuberculosis, caused by the pathogen Mycobacterium tuberculosis, is a worldwide public health threat. Mycobacterium tuberculosis is capable of resisting various stresses in host cells, including high levels of ROS and copper ions. To better understand the resistance mechanisms of mycobacteria to copper, we generated a copper-resistant strain of Mycobacterium smegmatis, mc(2)155-Cu from the selection of copper sulfate treated-bacteria. The mc(2)155-Cu strain has a 5-fold higher resistance to copper sulfate and a 2-fold higher resistance to isoniazid (INH) than its parental strain mc(2)155, respectively. Quantitative proteomics was carried out to find differentially expressed proteins between mc(2)155 and mc(2)155-Cu. Among 345 differentially expressed proteins, copper-translocating P-type ATPase was up-regulated, while all other ABC transporters were down-regulated in mc(2)155-Cu, suggesting copper-translocating P-type ATPase plays a crucial role in copper resistance. Results also indicated that the down-regulation of metabolic enzymes and decreases in cellular NAD, FAD, mycothiol, and glutamine levels in mc(2)155-Cu were responsible for its slowing growth rate as compared to mc(2)155. Down-regulation of KatG2 expression in both protein and mRNA levels indicates the co-evolution of copper and INH resistance in copper resistance bacteria, and provides new evidence to understanding of the molecular mechanisms of survival of mycobacteria under stress conditions. |
format | Online Article Text |
id | pubmed-4452738 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-44527382015-06-09 Proteomic Analysis of Drug-Resistant Mycobacteria: Co-Evolution of Copper and INH Resistance Chen, Yuling Yang, Fan Sun, Zhongyuan Wang, Qingtao Mi, Kaixia Deng, Haiteng PLoS One Research Article Tuberculosis, caused by the pathogen Mycobacterium tuberculosis, is a worldwide public health threat. Mycobacterium tuberculosis is capable of resisting various stresses in host cells, including high levels of ROS and copper ions. To better understand the resistance mechanisms of mycobacteria to copper, we generated a copper-resistant strain of Mycobacterium smegmatis, mc(2)155-Cu from the selection of copper sulfate treated-bacteria. The mc(2)155-Cu strain has a 5-fold higher resistance to copper sulfate and a 2-fold higher resistance to isoniazid (INH) than its parental strain mc(2)155, respectively. Quantitative proteomics was carried out to find differentially expressed proteins between mc(2)155 and mc(2)155-Cu. Among 345 differentially expressed proteins, copper-translocating P-type ATPase was up-regulated, while all other ABC transporters were down-regulated in mc(2)155-Cu, suggesting copper-translocating P-type ATPase plays a crucial role in copper resistance. Results also indicated that the down-regulation of metabolic enzymes and decreases in cellular NAD, FAD, mycothiol, and glutamine levels in mc(2)155-Cu were responsible for its slowing growth rate as compared to mc(2)155. Down-regulation of KatG2 expression in both protein and mRNA levels indicates the co-evolution of copper and INH resistance in copper resistance bacteria, and provides new evidence to understanding of the molecular mechanisms of survival of mycobacteria under stress conditions. Public Library of Science 2015-06-02 /pmc/articles/PMC4452738/ /pubmed/26035302 http://dx.doi.org/10.1371/journal.pone.0127788 Text en © 2015 Chen et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Chen, Yuling Yang, Fan Sun, Zhongyuan Wang, Qingtao Mi, Kaixia Deng, Haiteng Proteomic Analysis of Drug-Resistant Mycobacteria: Co-Evolution of Copper and INH Resistance |
title | Proteomic Analysis of Drug-Resistant Mycobacteria: Co-Evolution of Copper and INH Resistance |
title_full | Proteomic Analysis of Drug-Resistant Mycobacteria: Co-Evolution of Copper and INH Resistance |
title_fullStr | Proteomic Analysis of Drug-Resistant Mycobacteria: Co-Evolution of Copper and INH Resistance |
title_full_unstemmed | Proteomic Analysis of Drug-Resistant Mycobacteria: Co-Evolution of Copper and INH Resistance |
title_short | Proteomic Analysis of Drug-Resistant Mycobacteria: Co-Evolution of Copper and INH Resistance |
title_sort | proteomic analysis of drug-resistant mycobacteria: co-evolution of copper and inh resistance |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4452738/ https://www.ncbi.nlm.nih.gov/pubmed/26035302 http://dx.doi.org/10.1371/journal.pone.0127788 |
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