PRD-Containing Virulence Regulators (PCVRs) in Pathogenic Bacteria

Abstract

Bacterial pathogens rely on a complex network of regulatory proteins to adapt to hostile and nutrient-limiting host environments. The phosphoenolpyruvate phosphotransferase system (PTS) is a conserved pathway in bacteria that couples transport of sugars with phosphorylation to monitor host carbohydrate availability. A family of structurally homologous PTS-regulatory-domain-containing virulence regulators (PCVRs) has been recognized in divergent bacterial pathogens, including Streptococcus pyogenes Mga and Bacillus anthracis AtxA. These paradigm PCVRs undergo phosphorylation, potentially via the PTS, which impacts their dimerization and their activity. Recent work with predicted PCVRs from Streptococcus pneumoniae (MgaSpn) and Enterococcus faecalis (MafR) suggest they interact with DNA like nucleoid-associating proteins. Yet, Mga binds to promoter sequences as a homo-dimeric transcription factor, suggesting a bi-modal interaction with DNA. High-resolution crystal structures of 3 PCVRs have validated the domain structure, but also raised additional questions such as how ubiquitous are PCVRs, is PTS-mediated histidine phosphorylation via potential PCVRs widespread, do specific sugars signal through PCVRs, and do PCVRs interact with DNA both as transcription factors and nucleoid-associating proteins? Here, we will review known and putative PCVRs based on key domain and functional characteristics and consider their roles as both transcription factors and possibly chromatin-structuring proteins.

Characterisation of emergent toxigenic M1UKStreptococcus pyogenesand associated sublineages

“…This may be of importance since an absence of gldA activity may lead to a build-up of DHA, which when converted to methylglyoxal can be toxic (32). The upregulation of the PTS system is of interest since these are recognised to be key players in a phosphorelay process that maintains central carbon catabolite repression of many virulence systems in S. pyogenes (31, 33).…”

Apex Predator Nematodes and Meso-Predator Bacteria Consume Their Basal Insect Prey through Discrete Stages of Chemical Transformations

“…Additional overlapping regulon members revealed by the microarray includes genes (XNC1_2826 to XNC1_2828) predicted to encode an ascorbate superfamily enzyme II (EII) complex component of the phosphotransferase system sugar uptake and phosphorylation system. Such systems help coordinate the use of available carbon sources with cellular metabolism ( 34 , 35 ).…”

Expression of the Bacillus thuringiensis vip3A insecticidal toxin gene is activated at the onset of stationary phase by VipR, an autoregulated transcription factor

“…VipR presents structural homologies with the B. anthracis AtxA and the Streptococcus Mga transcriptional regulators belonging to the PRD-Containing Virulence Regulators (PCVR) family (44). These regulators are characterized by the presence of two N-terminal HTH domains, two centralized phosphoenolpyruvates: carbohydrate phosphotransferase system-regulated domains (PRD) and a C-terminal EIIB-like domain.…”

“…Since vipR expression depends on the activity of the VipR protein, this effect of the ∆spo0A mutation may be indirect through a derepression of vipR transcription by releasing the action of a repressor at the onset of stationary phase. Alternatively, the activity of VipR may depend on a functional activation.VipR presents structural homologies with the B. anthracis AtxA and theStreptococcus Mga transcriptional regulators belonging to the PRD-ContainingVirulence Regulators (PCVR) family(44). These regulators are characterized by the presence of two N-terminal HTH domains, two centralized phosphoenolpyruvates: carbohydrate phosphotransferase system-regulated domains (PRD) and a C-terminal EIIB-like domain.…”