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Zinc blocks SOS-induced antibiotic resistance via inhibition of RecA in Escherichia coli
Zinc inhibits the virulence of diarrheagenic E. coli by inducing the envelope stress response and inhibiting the SOS response. The SOS response is triggered by damage to bacterial DNA. In Shiga-toxigenic E. coli, the SOS response strongly induces the production of Shiga toxins (Stx) and of the bacte...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5440055/ https://www.ncbi.nlm.nih.gov/pubmed/28542496 http://dx.doi.org/10.1371/journal.pone.0178303 |
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author | Bunnell, Bryan E. Escobar, Jillian F. Bair, Kirsten L. Sutton, Mark D. Crane, John K. |
author_facet | Bunnell, Bryan E. Escobar, Jillian F. Bair, Kirsten L. Sutton, Mark D. Crane, John K. |
author_sort | Bunnell, Bryan E. |
collection | PubMed |
description | Zinc inhibits the virulence of diarrheagenic E. coli by inducing the envelope stress response and inhibiting the SOS response. The SOS response is triggered by damage to bacterial DNA. In Shiga-toxigenic E. coli, the SOS response strongly induces the production of Shiga toxins (Stx) and of the bacteriophages that encode the Stx genes. In E. coli, induction of the SOS response is accompanied by a higher mutation rate, called the mutator response, caused by a shift to error-prone DNA polymerases when DNA damage is too severe to be repaired by canonical DNA polymerases. Since zinc inhibited the other aspects of the SOS response, we hypothesized that zinc would also inhibit the mutator response, also known as hypermutation. We explored various different experimental paradigms to induce hypermutation triggered by the SOS response, and found that hypermutation was induced not just by classical inducers such as mitomycin C and the quinolone antibiotics, but also by antiviral drugs such as zidovudine and anti-cancer drugs such as 5-fluorouracil, 6-mercaptopurine, and azacytidine. Zinc salts inhibited the SOS response and the hypermutator phenomenon in E. coli as well as in Klebsiella pneumoniae, and was more effective in inhibiting the SOS response than other metals. We then attempted to determine the mechanism by which zinc, applied externally in the medium, inhibits hypermutation. Our results show that zinc interferes with the actions of RecA, and protects LexA from RecA-mediated cleavage, an early step in initiation of the SOS response. The SOS response may play a role in the development of antibiotic resistance and the effect of zinc suggests ways to prevent it. |
format | Online Article Text |
id | pubmed-5440055 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-54400552017-06-06 Zinc blocks SOS-induced antibiotic resistance via inhibition of RecA in Escherichia coli Bunnell, Bryan E. Escobar, Jillian F. Bair, Kirsten L. Sutton, Mark D. Crane, John K. PLoS One Research Article Zinc inhibits the virulence of diarrheagenic E. coli by inducing the envelope stress response and inhibiting the SOS response. The SOS response is triggered by damage to bacterial DNA. In Shiga-toxigenic E. coli, the SOS response strongly induces the production of Shiga toxins (Stx) and of the bacteriophages that encode the Stx genes. In E. coli, induction of the SOS response is accompanied by a higher mutation rate, called the mutator response, caused by a shift to error-prone DNA polymerases when DNA damage is too severe to be repaired by canonical DNA polymerases. Since zinc inhibited the other aspects of the SOS response, we hypothesized that zinc would also inhibit the mutator response, also known as hypermutation. We explored various different experimental paradigms to induce hypermutation triggered by the SOS response, and found that hypermutation was induced not just by classical inducers such as mitomycin C and the quinolone antibiotics, but also by antiviral drugs such as zidovudine and anti-cancer drugs such as 5-fluorouracil, 6-mercaptopurine, and azacytidine. Zinc salts inhibited the SOS response and the hypermutator phenomenon in E. coli as well as in Klebsiella pneumoniae, and was more effective in inhibiting the SOS response than other metals. We then attempted to determine the mechanism by which zinc, applied externally in the medium, inhibits hypermutation. Our results show that zinc interferes with the actions of RecA, and protects LexA from RecA-mediated cleavage, an early step in initiation of the SOS response. The SOS response may play a role in the development of antibiotic resistance and the effect of zinc suggests ways to prevent it. Public Library of Science 2017-05-22 /pmc/articles/PMC5440055/ /pubmed/28542496 http://dx.doi.org/10.1371/journal.pone.0178303 Text en © 2017 Bunnell 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 (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Bunnell, Bryan E. Escobar, Jillian F. Bair, Kirsten L. Sutton, Mark D. Crane, John K. Zinc blocks SOS-induced antibiotic resistance via inhibition of RecA in Escherichia coli |
title | Zinc blocks SOS-induced antibiotic resistance via inhibition of RecA in Escherichia coli |
title_full | Zinc blocks SOS-induced antibiotic resistance via inhibition of RecA in Escherichia coli |
title_fullStr | Zinc blocks SOS-induced antibiotic resistance via inhibition of RecA in Escherichia coli |
title_full_unstemmed | Zinc blocks SOS-induced antibiotic resistance via inhibition of RecA in Escherichia coli |
title_short | Zinc blocks SOS-induced antibiotic resistance via inhibition of RecA in Escherichia coli |
title_sort | zinc blocks sos-induced antibiotic resistance via inhibition of reca in escherichia coli |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5440055/ https://www.ncbi.nlm.nih.gov/pubmed/28542496 http://dx.doi.org/10.1371/journal.pone.0178303 |
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