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Mutations in bdcA and valS Correlate with Quinolone Resistance in Wastewater Escherichia coli

Single mutations can confer resistance to antibiotics. Identifying such mutations can help to develop and improve drugs. Here, we systematically screen for candidate quinolone resistance-conferring mutations. We sequenced highly diverse wastewater E. coli and performed a genome-wide association stud...

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Autores principales: Malekian, Negin, Al-Fatlawi, Ali, Berendonk, Thomas U., Schroeder, Michael
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8200043/
https://www.ncbi.nlm.nih.gov/pubmed/34199768
http://dx.doi.org/10.3390/ijms22116063
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author Malekian, Negin
Al-Fatlawi, Ali
Berendonk, Thomas U.
Schroeder, Michael
author_facet Malekian, Negin
Al-Fatlawi, Ali
Berendonk, Thomas U.
Schroeder, Michael
author_sort Malekian, Negin
collection PubMed
description Single mutations can confer resistance to antibiotics. Identifying such mutations can help to develop and improve drugs. Here, we systematically screen for candidate quinolone resistance-conferring mutations. We sequenced highly diverse wastewater E. coli and performed a genome-wide association study (GWAS) to determine associations between over 200,000 mutations and quinolone resistance phenotypes. We uncovered 13 statistically significant mutations including 1 located at the active site of the biofilm dispersal gene bdcA and 6 silent mutations in the aminoacyl-tRNA synthetase valS. The study also recovered the known mutations in the topoisomerases gyrase (gyrA) and topoisomerase IV (parC). In summary, we demonstrate that GWAS effectively and comprehensively identifies resistance mutations without a priori knowledge of targets and mode of action. The results suggest that mutations in the bdcA and valS genes, which are involved in biofilm dispersal and translation, may lead to novel resistance mechanisms.
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spelling pubmed-82000432021-06-14 Mutations in bdcA and valS Correlate with Quinolone Resistance in Wastewater Escherichia coli Malekian, Negin Al-Fatlawi, Ali Berendonk, Thomas U. Schroeder, Michael Int J Mol Sci Article Single mutations can confer resistance to antibiotics. Identifying such mutations can help to develop and improve drugs. Here, we systematically screen for candidate quinolone resistance-conferring mutations. We sequenced highly diverse wastewater E. coli and performed a genome-wide association study (GWAS) to determine associations between over 200,000 mutations and quinolone resistance phenotypes. We uncovered 13 statistically significant mutations including 1 located at the active site of the biofilm dispersal gene bdcA and 6 silent mutations in the aminoacyl-tRNA synthetase valS. The study also recovered the known mutations in the topoisomerases gyrase (gyrA) and topoisomerase IV (parC). In summary, we demonstrate that GWAS effectively and comprehensively identifies resistance mutations without a priori knowledge of targets and mode of action. The results suggest that mutations in the bdcA and valS genes, which are involved in biofilm dispersal and translation, may lead to novel resistance mechanisms. MDPI 2021-06-04 /pmc/articles/PMC8200043/ /pubmed/34199768 http://dx.doi.org/10.3390/ijms22116063 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Malekian, Negin
Al-Fatlawi, Ali
Berendonk, Thomas U.
Schroeder, Michael
Mutations in bdcA and valS Correlate with Quinolone Resistance in Wastewater Escherichia coli
title Mutations in bdcA and valS Correlate with Quinolone Resistance in Wastewater Escherichia coli
title_full Mutations in bdcA and valS Correlate with Quinolone Resistance in Wastewater Escherichia coli
title_fullStr Mutations in bdcA and valS Correlate with Quinolone Resistance in Wastewater Escherichia coli
title_full_unstemmed Mutations in bdcA and valS Correlate with Quinolone Resistance in Wastewater Escherichia coli
title_short Mutations in bdcA and valS Correlate with Quinolone Resistance in Wastewater Escherichia coli
title_sort mutations in bdca and vals correlate with quinolone resistance in wastewater escherichia coli
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8200043/
https://www.ncbi.nlm.nih.gov/pubmed/34199768
http://dx.doi.org/10.3390/ijms22116063
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