Back to Search
Start Over
Quorum Sensing Regulation of a Major Facilitator Superfamily Transporter Affects Multiple Streptococcal Virulence Factors.
- Source :
-
Journal of bacteriology [J Bacteriol] 2022 Sep 20; Vol. 204 (9), pp. e0017622. Date of Electronic Publication: 2022 Aug 08. - Publication Year :
- 2022
-
Abstract
- Cell-cell signaling mediated by Rgg-family transcription factors and their cognate pheromones is conserved in Firmicutes , including all streptococci. In Streptococcus pyogenes, or group A strep (GAS), one of these systems, the Rgg2/3 quorum sensing (QS) system, has been shown to regulate phenotypes, including cellular aggregation and biofilm formation, lysozyme resistance, and macrophage immunosuppression. Here, we show the abundance of several secreted virulence factors (streptolysin O, SpyCEP, and M protein) decreases upon induction of QS. The main mechanism underlying the changes in protein levels appears to be transcriptional, occurs downstream of the QS circuit, and is dysregulated by the deletion of an Rgg2/3 QS-regulated major facilitator superfamily (MFS) transporter. Additionally, we identify this MFS transporter as the factor responsible for a previously observed increase in aminoglycoside sensitivity in QS-induced cells. IMPORTANCE The production of virulence factors is a tightly regulated process in bacterial pathogens. Efforts to elucidate the mechanisms by which genes are regulated may advance the understanding of factors influencing pathogen behavior or cellular physiology. This work finds expression of a major facilitator superfamily (MFS) transporter, which is governed by a quorum sensing (QS) system, impacts the expression of multiple virulence factors and accounts for QS-dependent antibiotic susceptibility. Although the mechanism underlying this effect is not clear, MFS orthologs with high sequence similarity from S. pneumoniae and S. porcinus were unable to substitute indicating substrate specificity of the GAS MFS gene. These findings demonstrate novel associations between expression of a transmembrane transporter and virulence factor expression and aminoglycoside transport.
- Subjects :
- Aminoglycosides pharmacology
Anti-Bacterial Agents pharmacology
Gene Expression Regulation, Bacterial
Humans
Membrane Transport Proteins genetics
Membrane Transport Proteins metabolism
Muramidase metabolism
Pheromones metabolism
Transcription Factors metabolism
Virulence Factors genetics
Quorum Sensing physiology
Streptococcal Infections
Subjects
Details
- Language :
- English
- ISSN :
- 1098-5530
- Volume :
- 204
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Journal of bacteriology
- Publication Type :
- Academic Journal
- Accession number :
- 35938850
- Full Text :
- https://doi.org/10.1128/jb.00176-22