Role Of The Rpry Response Regulator Inp. Gingivaliscommunity Development And Virulence

Porphyromonas gingivalisexpresses a limited number of two-component systems, including RprY, an orphan response regulator which lacks a cognate sensor kinase. In this study, we examined cross-phosphorylation of RprY on tyrosine residues and its importance for RprY function. We show that RprY reacts with phosphotyrosine antibodies, and found that the tyrosine (Y) residue at position 41 is predicted to be solvent accessible. Loss of RprY increased the level of heterotypic community development withStreptococcus gordonii, and the community-suppressive function of RprY required Y41. Expression of the Mfa1 fimbrial adhesin was increased in therprYmutant and in the mutant complemented withrprYcontaining a Y41F mutation. In a microscale thermophoresis assay, recombinant RprY protein bound to the promoter region ofmfa1, and binding was diminished with RprY containing the Y41F substitution. RprY was required for virulence ofP. gingivalisin a murine model of alveolar bone loss. Transcriptional profiling indicated that RprY can control the expression of genes encoding the type IX secretion system (T9SS) machinery and virulence factors secreted through the T9SS, including the gingipain proteases and peptidylarginine deiminase (PPAD). Collectively, these results establish the RprY response regulator as a component of the tyrosine phosphorylation regulon inP. gingivalis, which can independently control heterotypic community development through the Mfa1 fimbriae and virulence through the T9SS.