Cargando…

A DNA-Damage Inducible Gene Promotes the Formation of Antibiotic Persisters in Response to the Quorum Sensing Signaling Peptide in Streptococcus mutans

Bacteria use quorum sensing (QS) to communicate with each other via secreted small autoinducers produced by individuals. QS allows bacteria to display a unified response that benefits the species during adaptation to environment, colonization, and defense against competitors. In oral streptococci, t...

Descripción completa

Detalles Bibliográficos
Autores principales: Dufour, Delphine, Zhao, Haowei, Gong, Siew-Ging, Lévesque, Céline M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9408444/
https://www.ncbi.nlm.nih.gov/pubmed/36011345
http://dx.doi.org/10.3390/genes13081434
_version_ 1784774602586587136
author Dufour, Delphine
Zhao, Haowei
Gong, Siew-Ging
Lévesque, Céline M.
author_facet Dufour, Delphine
Zhao, Haowei
Gong, Siew-Ging
Lévesque, Céline M.
author_sort Dufour, Delphine
collection PubMed
description Bacteria use quorum sensing (QS) to communicate with each other via secreted small autoinducers produced by individuals. QS allows bacteria to display a unified response that benefits the species during adaptation to environment, colonization, and defense against competitors. In oral streptococci, the CSP-ComDE QS is an inducible DNA damage repair system that is pivotal for bacterial survival. In the oral pathogen Streptococcus mutans, the QS system positively influences the formation of antibiotic persisters, cells that can survive antibiotic attack by entering a non-proliferative state. We recently identified a novel gene, pep299, that is activated in the persister cell fraction induced by QS. In this study, we focused our investigation on the role of pep299, a gene encoding a bacteriocin-like peptide, in the formation of antibiotic persisters. Mutant Δ299, unable to produce Pep299, showed a dramatic reduction in the number of stress-induced persisters. Using a co-culture assay, we showed that cells overproducing pep299 induced the formation of persisters in the mutant, suggesting that Pep299 was actively secreted and detected by neighboring cells. Cells exposed to DNA damage conditions activated the gene expression of pep299. Interestingly, our results suggested that the pep299 gene was also involved in the regulation of a QS-inducible toxin–antitoxin system. Our study suggests that the pep299 gene is at the core of the triggered persistence phenotype in S. mutans, allowing cells to transition into a state of reduced metabolic activity and antibiotic tolerance.
format Online
Article
Text
id pubmed-9408444
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-94084442022-08-26 A DNA-Damage Inducible Gene Promotes the Formation of Antibiotic Persisters in Response to the Quorum Sensing Signaling Peptide in Streptococcus mutans Dufour, Delphine Zhao, Haowei Gong, Siew-Ging Lévesque, Céline M. Genes (Basel) Article Bacteria use quorum sensing (QS) to communicate with each other via secreted small autoinducers produced by individuals. QS allows bacteria to display a unified response that benefits the species during adaptation to environment, colonization, and defense against competitors. In oral streptococci, the CSP-ComDE QS is an inducible DNA damage repair system that is pivotal for bacterial survival. In the oral pathogen Streptococcus mutans, the QS system positively influences the formation of antibiotic persisters, cells that can survive antibiotic attack by entering a non-proliferative state. We recently identified a novel gene, pep299, that is activated in the persister cell fraction induced by QS. In this study, we focused our investigation on the role of pep299, a gene encoding a bacteriocin-like peptide, in the formation of antibiotic persisters. Mutant Δ299, unable to produce Pep299, showed a dramatic reduction in the number of stress-induced persisters. Using a co-culture assay, we showed that cells overproducing pep299 induced the formation of persisters in the mutant, suggesting that Pep299 was actively secreted and detected by neighboring cells. Cells exposed to DNA damage conditions activated the gene expression of pep299. Interestingly, our results suggested that the pep299 gene was also involved in the regulation of a QS-inducible toxin–antitoxin system. Our study suggests that the pep299 gene is at the core of the triggered persistence phenotype in S. mutans, allowing cells to transition into a state of reduced metabolic activity and antibiotic tolerance. MDPI 2022-08-12 /pmc/articles/PMC9408444/ /pubmed/36011345 http://dx.doi.org/10.3390/genes13081434 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
Dufour, Delphine
Zhao, Haowei
Gong, Siew-Ging
Lévesque, Céline M.
A DNA-Damage Inducible Gene Promotes the Formation of Antibiotic Persisters in Response to the Quorum Sensing Signaling Peptide in Streptococcus mutans
title A DNA-Damage Inducible Gene Promotes the Formation of Antibiotic Persisters in Response to the Quorum Sensing Signaling Peptide in Streptococcus mutans
title_full A DNA-Damage Inducible Gene Promotes the Formation of Antibiotic Persisters in Response to the Quorum Sensing Signaling Peptide in Streptococcus mutans
title_fullStr A DNA-Damage Inducible Gene Promotes the Formation of Antibiotic Persisters in Response to the Quorum Sensing Signaling Peptide in Streptococcus mutans
title_full_unstemmed A DNA-Damage Inducible Gene Promotes the Formation of Antibiotic Persisters in Response to the Quorum Sensing Signaling Peptide in Streptococcus mutans
title_short A DNA-Damage Inducible Gene Promotes the Formation of Antibiotic Persisters in Response to the Quorum Sensing Signaling Peptide in Streptococcus mutans
title_sort dna-damage inducible gene promotes the formation of antibiotic persisters in response to the quorum sensing signaling peptide in streptococcus mutans
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9408444/
https://www.ncbi.nlm.nih.gov/pubmed/36011345
http://dx.doi.org/10.3390/genes13081434
work_keys_str_mv AT dufourdelphine adnadamageinduciblegenepromotestheformationofantibioticpersistersinresponsetothequorumsensingsignalingpeptideinstreptococcusmutans
AT zhaohaowei adnadamageinduciblegenepromotestheformationofantibioticpersistersinresponsetothequorumsensingsignalingpeptideinstreptococcusmutans
AT gongsiewging adnadamageinduciblegenepromotestheformationofantibioticpersistersinresponsetothequorumsensingsignalingpeptideinstreptococcusmutans
AT levesquecelinem adnadamageinduciblegenepromotestheformationofantibioticpersistersinresponsetothequorumsensingsignalingpeptideinstreptococcusmutans
AT dufourdelphine dnadamageinduciblegenepromotestheformationofantibioticpersistersinresponsetothequorumsensingsignalingpeptideinstreptococcusmutans
AT zhaohaowei dnadamageinduciblegenepromotestheformationofantibioticpersistersinresponsetothequorumsensingsignalingpeptideinstreptococcusmutans
AT gongsiewging dnadamageinduciblegenepromotestheformationofantibioticpersistersinresponsetothequorumsensingsignalingpeptideinstreptococcusmutans
AT levesquecelinem dnadamageinduciblegenepromotestheformationofantibioticpersistersinresponsetothequorumsensingsignalingpeptideinstreptococcusmutans