Dataset Information

Carbon catabolite repression on the Rgg2/3 quorum sensing system in Streptococcus pyogenes is mediated by PTS^Man and Mga.

ABSTRACT: Streptococcus pyogenes, also known as group A Streptococcus or GAS, is a human-restricted pathogen causing a diverse array of infections. The ability to adapt to different niches requires GAS to adjust gene expression in response to environmental cues. We previously identified the abundance of biometals and carbohydrates led to natural induction of the Rgg2/3 cell-cell communication system (quorum sensing, QS). Here we determined the mechanism by which the Rgg2/3 QS system is stimulated exclusively by mannose and repressed by glucose, a phenomenon known as carbon catabolite repression (CCR). Instead of carbon catabolite protein A, the primary mediator of CCR in Gram-positive bacteria; CCR of Rgg2/3 requires the PTS regulatory domain (PRD)-containing transcriptional regulator Mga. Deletion of Mga led to carbohydrate-independent activation of Rgg2/3 by down-regulating rgg3, the QS repressor. Through phosphoablative and phosphomimetic substitutions within Mga PRDs, we demonstrated that selective phosphorylation of PRD1 conferred repression of the Rgg2/3 system. Moreover, given the carbohydrate specificity mediating Mga-dependent governance over Rgg2/3, we tested mannose-specific PTS components and found the EIIA/B subunit ManL was required for Mga-dependent repression. These findings provide newfound connections between PTS^Man , Mga, and QS, and further demonstrate that Mga is a central regulatory nexus for integrating nutritional status and virulence.

SUBMITTER: Woo JKK

PROVIDER: S-EPMC8844239 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

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Carbon catabolite repression on the Rgg2/3 quorum sensing system in Streptococcus pyogenes is mediated by PTS<sup>Man</sup> and Mga.

Woo Jerry K K JKK McIver Kevin S KS Federle Michael J MJ

Molecular microbiology 20220103 2

Streptococcus pyogenes, also known as group A Streptococcus or GAS, is a human-restricted pathogen causing a diverse array of infections. The ability to adapt to different niches requires GAS to adjust gene expression in response to environmental cues. We previously identified the abundance of biometals and carbohydrates led to natural induction of the Rgg2/3 cell-cell communication system (quorum sensing, QS). Here we determined the mechanism by which the Rgg2/3 QS system is stimulated exclusiv ...[more]

PMID: 34923680

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Project description:Streptococcus pyogenes, otherwise known as Group A Streptococcus (GAS), is an important and highly adaptable human pathogen with the ability to cause both superficial and severe diseases. Understanding how S. pyogenes senses and responds to its environment will likely aid in determining how it causes a breadth of diseases. One regulatory network involved in GAS's ability to sense and respond to the changing environment is the Rgg2/3 quorum sensing (QS) system, which responds to metal and carbohydrate availability and regulates changes to the bacterial surface. To better understand the impact of Rgg2/3 QS on S. pyogenes physiology, we performed RNA-seq and tandem mass tag (TMT)-LC-MS/MS analysis on cells in which this system was induced with short hydrophobic peptide (SHP) pheromone or disrupted. Primary findings confirmed that pheromone stimulation in wild-type cultures is limited to the induction of operons whose promoters contain previously determined Rgg2/3 binding sequences. However, a deletion mutant of rgg3, a strain that endogenously produces elevated amounts of pheromone, led to extended alterations of the transcriptome and proteome, ostensibly by stress-induced pathways. Under such exaggerated pheromone conditions, a connection was identified between Rgg2/3 and the stringent response. Mutation of relA, the bifunctional guanosine tetra- and penta-phosphate nucleoside synthetase/hydrolase, and alarmone synthase genes sasA and sasB, impacted culture doubling times and disabled induction of Rgg2/3 in response to mannose, while manipulation of Rgg2/3 signaling modestly altered nucleotide levels. Our findings indicate that excessive pheromone production or exposure places stress on GAS resulting in an indirect altered proteome and transcriptome beyond primary pheromone signaling. IMPORTANCE Streptococcus pyogenes causes several important human diseases. This study evaluates how the induction or disruption of a cell-cell communication system alters S. pyogenes's gene expression and, in extreme conditions, its physiology. Using transcriptomic and proteomic approaches, the results define the pheromone-dependent regulon of the Rgg2/3 quorum sensing system. In addition, we find that excessive pheromone stimulation, generated by genetic disruption of the Rgg2/3 system, leads to stress responses that are associated with the stringent response. Disruption of stringent response affects the ability of the cell-cell communication system to respond under normally inducing conditions. These findings assist in the determination of how S. pyogenes is impacted by and responds to nontraditional sources of stress.

Dataset Information

Carbon catabolite repression on the Rgg2/3 quorum sensing system in Streptococcus pyogenes is mediated by PTS^Man and Mga.

Publications

Carbon catabolite repression on the Rgg2/3 quorum sensing system in Streptococcus pyogenes is mediated by PTS<sup>Man</sup> and Mga.

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Dataset Information

Carbon catabolite repression on the Rgg2/3 quorum sensing system in Streptococcus pyogenes is mediated by PTSMan and Mga.

Publications

Carbon catabolite repression on the Rgg2/3 quorum sensing system in Streptococcus pyogenes is mediated by PTS<sup>Man</sup> and Mga.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Carbon catabolite repression on the Rgg2/3 quorum sensing system in Streptococcus pyogenes is mediated by PTS^Man and Mga.