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Vancomycin Activates σ(B) in Vancomycin-Resistant Staphylococcus aureus Resulting in the Enhancement of Cytotoxicity

The alternative transcription factor σ(B) is responsible for transcription in Staphylococcus aureus during the stress response. Many virulence-associated genes are directly or indirectly regulated by σ(B). We hypothesized that treatment with antibiotics may act as an environmental stressor that indu...

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Autores principales: Chen, Hong-Yi, Chen, Chien-Cheng, Fang, Chun-Sheng, Hsieh, Yi-Ting, Lin, Mei-Hui, Shu, Jwu-Ching
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3166330/
https://www.ncbi.nlm.nih.gov/pubmed/21912698
http://dx.doi.org/10.1371/journal.pone.0024472
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author Chen, Hong-Yi
Chen, Chien-Cheng
Fang, Chun-Sheng
Hsieh, Yi-Ting
Lin, Mei-Hui
Shu, Jwu-Ching
author_facet Chen, Hong-Yi
Chen, Chien-Cheng
Fang, Chun-Sheng
Hsieh, Yi-Ting
Lin, Mei-Hui
Shu, Jwu-Ching
author_sort Chen, Hong-Yi
collection PubMed
description The alternative transcription factor σ(B) is responsible for transcription in Staphylococcus aureus during the stress response. Many virulence-associated genes are directly or indirectly regulated by σ(B). We hypothesized that treatment with antibiotics may act as an environmental stressor that induces σ(B) activity in antibiotic-resistant strains. Several antibiotics with distinct modes of action, including ampicillin (12 µg/ml), vancomycin (16 or 32 µg/ml), chloramphenicol (15 µg/ml), ciprofloxacin (0.25 µg/ml), and sulfamethoxazole/trimethoprim (SXT, 0.8 µg/ml), were investigated for their ability to activate this transcription factor. We were especially interested in the stress response in vancomycin-resistant S. aureus (VRSA) strains treated with vancomycin. The transcription levels of selected genes associated with virulence were also measured. Real-time quantitative reverse transcription PCR was employed to evaluate gene transcription levels. Contact hemolytic and cytotoxicity assays were used to evaluate cell damage following antibiotic treatment. Antibiotics that target the cell wall (vancomycin and ampicillin) and SXT induced σ(B) activity in VRSA strains. Expression of σ(B)-regulated virulence genes, including hla and fnbA, was associated with the vancomycin-induced σ(B) activity in VRSA strains and the increase in cytotoxicity upon vancomycin treatment. These effects were not observed in the sigB-deficient strain but were observed in the complemented strain. We demonstrate that sub-minimum inhibitory concentration (sub-MIC) levels of antibiotics act as environmental stressors and activate the stress response sigma factor, σ(B). The improper use of antibiotics may alter the expression of virulence factors through the activation of σ(B) in drug-resistant strains of S. aureus and lead to worse clinical outcomes.
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spelling pubmed-31663302011-09-12 Vancomycin Activates σ(B) in Vancomycin-Resistant Staphylococcus aureus Resulting in the Enhancement of Cytotoxicity Chen, Hong-Yi Chen, Chien-Cheng Fang, Chun-Sheng Hsieh, Yi-Ting Lin, Mei-Hui Shu, Jwu-Ching PLoS One Research Article The alternative transcription factor σ(B) is responsible for transcription in Staphylococcus aureus during the stress response. Many virulence-associated genes are directly or indirectly regulated by σ(B). We hypothesized that treatment with antibiotics may act as an environmental stressor that induces σ(B) activity in antibiotic-resistant strains. Several antibiotics with distinct modes of action, including ampicillin (12 µg/ml), vancomycin (16 or 32 µg/ml), chloramphenicol (15 µg/ml), ciprofloxacin (0.25 µg/ml), and sulfamethoxazole/trimethoprim (SXT, 0.8 µg/ml), were investigated for their ability to activate this transcription factor. We were especially interested in the stress response in vancomycin-resistant S. aureus (VRSA) strains treated with vancomycin. The transcription levels of selected genes associated with virulence were also measured. Real-time quantitative reverse transcription PCR was employed to evaluate gene transcription levels. Contact hemolytic and cytotoxicity assays were used to evaluate cell damage following antibiotic treatment. Antibiotics that target the cell wall (vancomycin and ampicillin) and SXT induced σ(B) activity in VRSA strains. Expression of σ(B)-regulated virulence genes, including hla and fnbA, was associated with the vancomycin-induced σ(B) activity in VRSA strains and the increase in cytotoxicity upon vancomycin treatment. These effects were not observed in the sigB-deficient strain but were observed in the complemented strain. We demonstrate that sub-minimum inhibitory concentration (sub-MIC) levels of antibiotics act as environmental stressors and activate the stress response sigma factor, σ(B). The improper use of antibiotics may alter the expression of virulence factors through the activation of σ(B) in drug-resistant strains of S. aureus and lead to worse clinical outcomes. Public Library of Science 2011-09-02 /pmc/articles/PMC3166330/ /pubmed/21912698 http://dx.doi.org/10.1371/journal.pone.0024472 Text en 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, Hong-Yi
Chen, Chien-Cheng
Fang, Chun-Sheng
Hsieh, Yi-Ting
Lin, Mei-Hui
Shu, Jwu-Ching
Vancomycin Activates σ(B) in Vancomycin-Resistant Staphylococcus aureus Resulting in the Enhancement of Cytotoxicity
title Vancomycin Activates σ(B) in Vancomycin-Resistant Staphylococcus aureus Resulting in the Enhancement of Cytotoxicity
title_full Vancomycin Activates σ(B) in Vancomycin-Resistant Staphylococcus aureus Resulting in the Enhancement of Cytotoxicity
title_fullStr Vancomycin Activates σ(B) in Vancomycin-Resistant Staphylococcus aureus Resulting in the Enhancement of Cytotoxicity
title_full_unstemmed Vancomycin Activates σ(B) in Vancomycin-Resistant Staphylococcus aureus Resulting in the Enhancement of Cytotoxicity
title_short Vancomycin Activates σ(B) in Vancomycin-Resistant Staphylococcus aureus Resulting in the Enhancement of Cytotoxicity
title_sort vancomycin activates σ(b) in vancomycin-resistant staphylococcus aureus resulting in the enhancement of cytotoxicity
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3166330/
https://www.ncbi.nlm.nih.gov/pubmed/21912698
http://dx.doi.org/10.1371/journal.pone.0024472
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