Pspc Domain-Containing Protein (Pcp) Determines Streptococcus Mutans Biofilm Formation Through Bacterial Extracellular Dna Release And Platelet Adhesion In Experimental Endocarditis

Bacterial extracellular DNA (eDNA) and activated platelets have been found to contribute to biofilm formation by Streptococcus mutans on injured heart valves to induce infective endocarditis (IE), yet the bacterial component directly responsible for biofilm formation or platelet adhesion remains unclear. Using in vivo survival assays coupled with microarray analysis, the present study identified a LiaR-regulated PspC domain-containing protein (PCP) in S. mutans that mediates bacterial biofilm formation in vivo. Reverse transcriptase- and chromatin immunoprecipitation-polymerase chain reaction assays confirmed the regulation of pcp by LiaR, while PCP is well-preserved among streptococcal pathogens. Deficiency of pcp reduced in vitro and in vivo biofilm formation and released the eDNA inside bacteria floe along with reduced bacterial platelet adhesion capacity in a fibrinogen-dependent manner. Therefore, LiaR-regulated PCP alone could determine release of bacterial eDNA and binding to platelets, thus contributing to biofilm formation in S. mutans-induced IE.Author summaryPhage shock proteins (Psps) are well-characterized in Gram-negative bacteria, yet their roles in Gram-positive were yet unknown. Interestingly, we found a PspC homolog [named PspC domain-containing protein (PCP) in this study] that is well preserved and conserved among pathogenic streptococci, including S. pneumonia and group A and group B streptococci. Using a rat experimental endocarditis infection model and S. mutans as a representative pathogen, we demonstrated PCP alone could mediate bacterial colonization and biofilm formation in situ. Therefore, PCP codes for an essential gene controlling biofilm formation in vivo for S. mutans and possibly other pathogenic streptococci.