Cargando…
RecA and Specialized Error-Prone DNA Polymerases Are Not Required for Mutagenesis and Antibiotic Resistance Induced by Fluoroquinolones in Pseudomonas aeruginosa
To cope with stressful conditions, including antibiotic exposure, bacteria activate the SOS response, a pathway that induces error-prone DNA repair and mutagenesis mechanisms. In most bacteria, the SOS response relies on the transcriptional repressor LexA and the co-protease RecA, the latter being a...
Autores principales: | , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8944484/ https://www.ncbi.nlm.nih.gov/pubmed/35326787 http://dx.doi.org/10.3390/antibiotics11030325 |
_version_ | 1784673725894885376 |
---|---|
author | Mercolino, Jessica Lo Sciuto, Alessandra Spinnato, Maria Concetta Rampioni, Giordano Imperi, Francesco |
author_facet | Mercolino, Jessica Lo Sciuto, Alessandra Spinnato, Maria Concetta Rampioni, Giordano Imperi, Francesco |
author_sort | Mercolino, Jessica |
collection | PubMed |
description | To cope with stressful conditions, including antibiotic exposure, bacteria activate the SOS response, a pathway that induces error-prone DNA repair and mutagenesis mechanisms. In most bacteria, the SOS response relies on the transcriptional repressor LexA and the co-protease RecA, the latter being also involved in homologous recombination. The role of the SOS response in stress- and antibiotic-induced mutagenesis has been characterized in detail in the model organism Escherichia coli. However, its effect on antibiotic resistance in the human pathogen Pseudomonas aeruginosa is less clear. Here, we analyzed a recA deletion mutant and confirmed, by conjugation and gene expression assays, that RecA is required for homologous recombination and SOS response induction in P. aeruginosa. MIC assays demonstrated that RecA affects P. aeruginosa resistance only towards fluoroquinolones and genotoxic agents. The comparison of antibiotic-resistant mutant frequency between treated and untreated cultures revealed that, among the antibiotics tested, only fluoroquinolones induced mutagenesis in P. aeruginosa. Notably, both RecA and error-prone DNA polymerases were found to be dispensable for this process. These data demonstrate that the SOS response is not required for antibiotic-induced mutagenesis in P. aeruginosa, suggesting that RecA inhibition is not a suitable strategy to target antibiotic-induced emergence of resistance in this pathogen. |
format | Online Article Text |
id | pubmed-8944484 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-89444842022-03-25 RecA and Specialized Error-Prone DNA Polymerases Are Not Required for Mutagenesis and Antibiotic Resistance Induced by Fluoroquinolones in Pseudomonas aeruginosa Mercolino, Jessica Lo Sciuto, Alessandra Spinnato, Maria Concetta Rampioni, Giordano Imperi, Francesco Antibiotics (Basel) Article To cope with stressful conditions, including antibiotic exposure, bacteria activate the SOS response, a pathway that induces error-prone DNA repair and mutagenesis mechanisms. In most bacteria, the SOS response relies on the transcriptional repressor LexA and the co-protease RecA, the latter being also involved in homologous recombination. The role of the SOS response in stress- and antibiotic-induced mutagenesis has been characterized in detail in the model organism Escherichia coli. However, its effect on antibiotic resistance in the human pathogen Pseudomonas aeruginosa is less clear. Here, we analyzed a recA deletion mutant and confirmed, by conjugation and gene expression assays, that RecA is required for homologous recombination and SOS response induction in P. aeruginosa. MIC assays demonstrated that RecA affects P. aeruginosa resistance only towards fluoroquinolones and genotoxic agents. The comparison of antibiotic-resistant mutant frequency between treated and untreated cultures revealed that, among the antibiotics tested, only fluoroquinolones induced mutagenesis in P. aeruginosa. Notably, both RecA and error-prone DNA polymerases were found to be dispensable for this process. These data demonstrate that the SOS response is not required for antibiotic-induced mutagenesis in P. aeruginosa, suggesting that RecA inhibition is not a suitable strategy to target antibiotic-induced emergence of resistance in this pathogen. MDPI 2022-02-28 /pmc/articles/PMC8944484/ /pubmed/35326787 http://dx.doi.org/10.3390/antibiotics11030325 Text en © 2022 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 Mercolino, Jessica Lo Sciuto, Alessandra Spinnato, Maria Concetta Rampioni, Giordano Imperi, Francesco RecA and Specialized Error-Prone DNA Polymerases Are Not Required for Mutagenesis and Antibiotic Resistance Induced by Fluoroquinolones in Pseudomonas aeruginosa |
title | RecA and Specialized Error-Prone DNA Polymerases Are Not Required for Mutagenesis and Antibiotic Resistance Induced by Fluoroquinolones in Pseudomonas aeruginosa |
title_full | RecA and Specialized Error-Prone DNA Polymerases Are Not Required for Mutagenesis and Antibiotic Resistance Induced by Fluoroquinolones in Pseudomonas aeruginosa |
title_fullStr | RecA and Specialized Error-Prone DNA Polymerases Are Not Required for Mutagenesis and Antibiotic Resistance Induced by Fluoroquinolones in Pseudomonas aeruginosa |
title_full_unstemmed | RecA and Specialized Error-Prone DNA Polymerases Are Not Required for Mutagenesis and Antibiotic Resistance Induced by Fluoroquinolones in Pseudomonas aeruginosa |
title_short | RecA and Specialized Error-Prone DNA Polymerases Are Not Required for Mutagenesis and Antibiotic Resistance Induced by Fluoroquinolones in Pseudomonas aeruginosa |
title_sort | reca and specialized error-prone dna polymerases are not required for mutagenesis and antibiotic resistance induced by fluoroquinolones in pseudomonas aeruginosa |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8944484/ https://www.ncbi.nlm.nih.gov/pubmed/35326787 http://dx.doi.org/10.3390/antibiotics11030325 |
work_keys_str_mv | AT mercolinojessica recaandspecializederrorpronednapolymerasesarenotrequiredformutagenesisandantibioticresistanceinducedbyfluoroquinolonesinpseudomonasaeruginosa AT losciutoalessandra recaandspecializederrorpronednapolymerasesarenotrequiredformutagenesisandantibioticresistanceinducedbyfluoroquinolonesinpseudomonasaeruginosa AT spinnatomariaconcetta recaandspecializederrorpronednapolymerasesarenotrequiredformutagenesisandantibioticresistanceinducedbyfluoroquinolonesinpseudomonasaeruginosa AT rampionigiordano recaandspecializederrorpronednapolymerasesarenotrequiredformutagenesisandantibioticresistanceinducedbyfluoroquinolonesinpseudomonasaeruginosa AT imperifrancesco recaandspecializederrorpronednapolymerasesarenotrequiredformutagenesisandantibioticresistanceinducedbyfluoroquinolonesinpseudomonasaeruginosa |