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The type IX secretion system (T9SS) in <jats:styled-content style=\"fixed-case\"><jats:italic>P. gingivalis<\/jats:italic><\/jats:styled-content> secretes conserved C\u2010terminal 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\u2010component regulatory system, PorX\u2010PorY, an ECF sigma factor, SigP, and a T9SS cargo protein, PorA. As PorA has its own CTD, PorA is mainly localized as an A\u2010LPS\u2010bound form and PorV\u2010bound form on the cell surface. However, it remains unclear how PorA can activate the PorXY\u2010SigP signaling cascade. In this study, our results revealed that the CTD of PorA can activate the PorXY\u2010SigP 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.<\/jats:p>","DOI":"10.1111\/mmi.15363","type":"journal-article","created":{"date-parts":[[2025,4,8]],"date-time":"2025-04-08T07:02:52Z","timestamp":1744095772000},"page":"569-585","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["<scp>PorA<\/scp> of the Type <scp>IX<\/scp> Secretion Is a Ligand of the <scp>PorXY<\/scp> Two\u2010Component Regulatory System in <scp><i>Porphyromonas gingivalis<\/i><\/scp>"],"prefix":"10.1111","volume":"123","author":[{"given":"Momoko","family":"Ito","sequence":"first","affiliation":[{"name":"Department of Microbiology and Oral Infection, Graduate School of Biomedical Sciences Nagasaki University  Nagasaki Nagasaki Japan"},{"name":"Department of Pediatric Dentistry 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