| Title: | A tripartite toxin-antitoxin module induced by quorum sensing is associated with the persistence phenotype in Streptococcus mutans |
| Author(s): | Dufour D; Mankovskaia A; Chan Y; Motavaze K; Gong SG; Levesque CM; |
| Address: | "Faculty of Dentistry, University of Toronto, Toronto, ON, Canada. Department of Applied Oral Sciences, Faculty of Dentistry, The University of Hong Kong, Hong Kong, Hong Kong" |
| ISSN/ISBN: | 2041-1014 (Electronic) 2041-1006 (Linking) |
| Abstract: | "The oral pathogen Streptococcus mutans communicates using a canonical Gram-positive quorum sensing system, CSP-ComDE. The CSP pheromone already known to be involved in the development of genetic competence positively influences the formation of persisters, dormant variants of regular cells that are highly tolerant to antimicrobial therapy. It is now believed that the persistence phenotype is the end result of a stochastic switch in the expression of toxin-antitoxin (TA) modules. TAs consist of a pair of genes that encode two components, a stable toxin and its cognate labile antitoxin. Transcription analyses revealed that three core genes encoding a putative TA system, called SmuATR, were members of the S. mutans CSP regulon. We hypothesized that S. mutans is using its CSP-ComDE system as a deterministic mechanism for persister formation through the activation of smuATR locus. We showed here that the SmuATR system constitutes a novel tripartite type II TA system in which the smuA and smuT genes encode an antitoxin and a toxin, respectively, while SmuR is a transcriptional repressor involved in the autoregulation of the operon. Ectopic expression of SmuA - SmuT is associated with the CSP-inducible persistence phenotype. In contrast, overexpression of SmuT alone is bactericidal and causes membrane permeabilization. To our knowledge, SmuATR is the first functional chromosomal tripartite TA system shown to be induced by the bacterial quorum sensing system and involved in persister formation" |
| Keywords: | "Bacterial Proteins/*genetics/metabolism Gene Expression Regulation, Bacterial Operon *Quorum Sensing Streptococcus mutans/*genetics/physiology *Toxin-Antitoxin Systems Transcription Factors/genetics CSP pheromone persisters quorum sensing streptococci tox;" |
| Notes: | "MedlineDufour, Delphine Mankovskaia, Alexandra Chan, Yuki Motavaze, Kamyar Gong, Siew-Ging Levesque, Celine M eng Research Support, Non-U.S. Gov't Denmark 2018/10/10 Mol Oral Microbiol. 2018 Dec; 33(6):420-429. doi: 10.1111/omi.12245. Epub 2018 Oct 24" |
