<scp>PorA</scp> of the Type <scp>IX</scp> Secretion Is a Ligand of the <scp>PorXY</scp> Two‐Component Regulatory System in <scp><i>Porphyromonas gingivalis</i></scp>

Porphyromonas gingivalis is an important bacterium associated with chronic periodontitis. The type IX secretion system (T9SS) in P. gingivalis secretes conserved C-terminal domain (CTD) containing proteins, which are also called T9SS cargo proteins, including gingipain proteinases, to the cell surface and extracellular milieu. We have shown that gene expression of some T9SS component proteins is regulated by a two-component regulatory system, PorX-PorY, an ECF sigma factor, SigP, and a T9SS cargo protein, PorA. As PorA has its own CTD, PorA is mainly localized as an A-LPS-bound form and PorV-bound form on the cell surface. However, it remains unclear how PorA can activate the PorXY-SigP signaling cascade. In this study, our results revealed that the CTD of PorA can activate the PorXY-SigP signaling cascade via interaction with PorY. It is well known that the canonical role of CTD is to act as a secretion signal for T9SS protein export. In here, we propose a novel concept that the CTD of PorA can play a dual role: as a secretion signal directing the secretion of PorA and as a positive regulator of T9SS gene expression by binding to PorY in the periplasm.