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The plasmid‐borne quinolone resistance protein QnrB, a novel DnaA‐binding protein, increases the bacterial mutation rate by triggering DNA replication stress
Bacterial antibiotic resistance, a global health threat, is caused by plasmid transfer or genetic mutations. Quinolones are important antibiotics, partially because they are fully synthetic and resistance genes are unlikely to exist in nature; nonetheless, quinolone resistance proteins have been ide...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6617969/ https://www.ncbi.nlm.nih.gov/pubmed/30838726 http://dx.doi.org/10.1111/mmi.14235 |
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author | Li, Xiaojing Zhang, Yujiao Zhou, Xintong Hu, Xinling Zhou, Yixuan Liu, Di Maxwell, Anthony Mi, Kaixia |
author_facet | Li, Xiaojing Zhang, Yujiao Zhou, Xintong Hu, Xinling Zhou, Yixuan Liu, Di Maxwell, Anthony Mi, Kaixia |
author_sort | Li, Xiaojing |
collection | PubMed |
description | Bacterial antibiotic resistance, a global health threat, is caused by plasmid transfer or genetic mutations. Quinolones are important antibiotics, partially because they are fully synthetic and resistance genes are unlikely to exist in nature; nonetheless, quinolone resistance proteins have been identified. The mechanism by which plasmid‐borne quinolone resistance proteins promotes the selection of quinolone‐resistant mutants is unclear. Here, we show that QnrB increases the bacterial mutation rate. Transcriptomic and genome sequencing analyses showed that QnrB promoted gene abundance near the origin of replication (oriC). In addition, the QnrB expression level correlated with the replication origin to terminus (oriC/ter) ratio, indicating QnrB‐induced DNA replication stress. Our results also show that QnrB is a DnaA‐binding protein that may act as an activator of DNA replication initiation. Interaction of QnrB with DnaA promoted the formation of the DnaA‐oriC open complex, which leads to DNA replication over‐initiation. Our data indicate that plasmid‐borne QnrB increases bacterial mutation rates and that genetic changes can alleviate the fitness cost imposed by transmitted plasmids. Derivative mutations may impair antibiotic efficacy and threaten the value of antibiotic treatments. Enhanced understanding of how bacteria adapt to the antibiotic environment will lead to new therapeutic strategies for antibiotic‐resistant infections. |
format | Online Article Text |
id | pubmed-6617969 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-66179692019-07-22 The plasmid‐borne quinolone resistance protein QnrB, a novel DnaA‐binding protein, increases the bacterial mutation rate by triggering DNA replication stress Li, Xiaojing Zhang, Yujiao Zhou, Xintong Hu, Xinling Zhou, Yixuan Liu, Di Maxwell, Anthony Mi, Kaixia Mol Microbiol Research Articles Bacterial antibiotic resistance, a global health threat, is caused by plasmid transfer or genetic mutations. Quinolones are important antibiotics, partially because they are fully synthetic and resistance genes are unlikely to exist in nature; nonetheless, quinolone resistance proteins have been identified. The mechanism by which plasmid‐borne quinolone resistance proteins promotes the selection of quinolone‐resistant mutants is unclear. Here, we show that QnrB increases the bacterial mutation rate. Transcriptomic and genome sequencing analyses showed that QnrB promoted gene abundance near the origin of replication (oriC). In addition, the QnrB expression level correlated with the replication origin to terminus (oriC/ter) ratio, indicating QnrB‐induced DNA replication stress. Our results also show that QnrB is a DnaA‐binding protein that may act as an activator of DNA replication initiation. Interaction of QnrB with DnaA promoted the formation of the DnaA‐oriC open complex, which leads to DNA replication over‐initiation. Our data indicate that plasmid‐borne QnrB increases bacterial mutation rates and that genetic changes can alleviate the fitness cost imposed by transmitted plasmids. Derivative mutations may impair antibiotic efficacy and threaten the value of antibiotic treatments. Enhanced understanding of how bacteria adapt to the antibiotic environment will lead to new therapeutic strategies for antibiotic‐resistant infections. John Wiley and Sons Inc. 2019-03-27 2019-06 /pmc/articles/PMC6617969/ /pubmed/30838726 http://dx.doi.org/10.1111/mmi.14235 Text en © 2019 The Authors. Molecular Microbiology Published by John Wiley & Sons Ltd This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Articles Li, Xiaojing Zhang, Yujiao Zhou, Xintong Hu, Xinling Zhou, Yixuan Liu, Di Maxwell, Anthony Mi, Kaixia The plasmid‐borne quinolone resistance protein QnrB, a novel DnaA‐binding protein, increases the bacterial mutation rate by triggering DNA replication stress |
title | The plasmid‐borne quinolone resistance protein QnrB, a novel DnaA‐binding protein, increases the bacterial mutation rate by triggering DNA replication stress |
title_full | The plasmid‐borne quinolone resistance protein QnrB, a novel DnaA‐binding protein, increases the bacterial mutation rate by triggering DNA replication stress |
title_fullStr | The plasmid‐borne quinolone resistance protein QnrB, a novel DnaA‐binding protein, increases the bacterial mutation rate by triggering DNA replication stress |
title_full_unstemmed | The plasmid‐borne quinolone resistance protein QnrB, a novel DnaA‐binding protein, increases the bacterial mutation rate by triggering DNA replication stress |
title_short | The plasmid‐borne quinolone resistance protein QnrB, a novel DnaA‐binding protein, increases the bacterial mutation rate by triggering DNA replication stress |
title_sort | plasmid‐borne quinolone resistance protein qnrb, a novel dnaa‐binding protein, increases the bacterial mutation rate by triggering dna replication stress |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6617969/ https://www.ncbi.nlm.nih.gov/pubmed/30838726 http://dx.doi.org/10.1111/mmi.14235 |
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