Deficiency of BrpA in Streptococcus mutans reduces virulence in rat caries model

Abstract

Our recent studies have shown that BrpA in Streptococcus mutans plays a critical role in cell envelope biogenesis, stress responses, and biofilm formation. In this study, a 10-species consortium was used to assess how BrpA deficiency influences the establishment, persistence, and competitiveness of S. mutans during growth in a community under conditions typical of the oral cavity. Results showed that, like the wild-type, the brpA mutant was able to colonize and establish on the surfaces tested. Relative to the wild-type, however, the brpA mutant had a reduced ability to persist and grow in the 10-species consortium (P < .001). A rat caries model was also used to examine the effect of BrpA, as well as Psr, a BrpA paralog, on S. mutans cariogenicity. The results showed no major differences in infectivity between the wild-type and the brpA and psr mutants. Unlike the wild-type, however, infection with the brpA mutant, but not the psr mutant, showed no significant differences in both total numbers of carious lesions and caries severity, compared with the control group that received bacterial growth medium (P > .05). Metagenomic and quantitative polymerase chain reaction analysis showed that S. mutans infection caused major alterations in the composition of the rats' plaque microbiota and that significantly less S. mutans was identified in the rats infected with the brpA mutant compared with those infected with the wild-type and the psr mutant. These results further suggest that BrpA plays a critical role in S. mutans pathophysiology and that BrpA has potential as a therapeutic target in the modulation of S. mutans virulence.

CRISPR-cas3 of Salmonella Upregulates Bacterial Biofilm Formation and Virulence to Host Cells by Targeting Quorum-Sensing Systems

“…It has been well recognized that biofilm formation helps Salmonella to survive under adverse environment [71]. Importantly, biofilm formation is one of the important virulence determinants of Salmonella and is also associated with resistance against the response of the host immune system [72][73][74]. A previous study showed that biofilm formation was decreased in the Streptococcus mutants cas3 deficiency strain, encoding a type I-C CRISPR-Cas system [75].…”

The Impacts of Sortase A and the 4′-Phosphopantetheinyl Transferase Homolog Sfp on Streptococcus mutans Extracellular Membrane Vesicle Biogenesis

“…Also uniquely detected in sfp EMVs was BrpA. BrpA is a surface associated protein with important roles in cell envelope biogenesis, biofilm formation and virulence (Wen et al, 2006(Wen et al, , 2018. Deficiency of this protein in S. mutans impairs biofilm formation (Wen et al, 2006), affects cell division and membrane fatty acid composition thereby reducing acid tolerance, and significantly diminishing the organism's ability to compete within polymicrobial communities and to cause dental caries in a rat model (Wen et al, 2018).…”

“…To gain insight into the role S. mutans EMVs play in delivering specific protein cargo to the extracellular environment, proteins exclusive to the EMVs or with a fold-change of log2 > 1.5 in EMVs compared to CMs, were tabulated ( Table 1). These results illustrate that S. mutans MV cargo contributes to cell wall development and cell architecture (Wen et al, 2018), bacterial adhesion (Matsumoto-Nakano, 2018), biofilm cell density (Besingi et al, 2017) and matrix development (Bowen and Koo, 2011), and intermolecular competition with other microorganisms (Hamada and Ooshima, 1975). Among the over-represented proteins in the sfp EMVs were BacA (Smu_1340) and BacA2 (Smu_1342) that similar to Sfp are also encoded by genes within the TnSmu2 genomic island.…”

Deficiency of MecA in Streptococcus mutans Causes Major Defects in Cell Envelope Biogenesis, Cell Division, and Biofilm Formation

“…S. mutans is not known to possess copious cell wall teichoic acids, and key members of the biosynthesis pathway have not yet been identified ( De et al, 2017 ). However, our recent studies have generated evidence that the bacterium also produces phosphate containing polymers besides RGP and whose attachment to the cell wall are catalyzed by BrpA and Psr, two paralogs of the LytR/CpsA/Psr family (LCP) proteins ( De et al, 2017 ; Wen et al, 2018 ). Morphologically, the MecA-deficient mutants resembles the rgpG / brpA / psr triple mutants, which also feature giant cells and multiple asymmetric septa ( De et al, 2017 ).…”