Investigations into a new secretion pathway for the export of gingipain from Porphyromonas gingivalislis

Abstract

Type IX Secretion System (T9SS) is a novel protein secretion pathway for numerous virulence factors in Porphyromonas gingivalis–the “keystone” pathogen in chronic periodontitis. The known substrates of this secretion system, including the major virulence factor, gingipains, carry a conserved C-terminal domain (CTD) which has been found to be cleaved during the translocation process and function as a recognition signal for the T9SS. However, multiple alignment of various CTDs failed to define a consensus sequence at the putative CTD processing site. In this doctoral candidature, we carried out site-directed mutagenesis and subtitutional manipulation of the β-hairpin fold of the Ig-like subdomain (IgLD), to show that the CTD recognition and cleavage at the site was dependent on the junction conformation between the CTD and adjecent IgLD instead of a specific residue or local sequence. Further, a novel CTD protein PG1604 was identified to be essential for maturation and secretion of gingipain and shown to be a new component of T9SS. Investigation into the secretion mechanism and novel components identification in this study may broaden our insights to this secretion system and provide opportunities to control the maturation of virulence factors from P. gingivalis in the treatment of periodontal disease.