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...

Descripción completa

Detalles Bibliográficos
Autores principales: Mercolino, Jessica, Lo Sciuto, Alessandra, Spinnato, Maria Concetta, Rampioni, Giordano, Imperi, Francesco
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