Project Summary Sialic acids (SA) describe a complex class of nine-carbon sugar acids that exist primarily as terminal moieties on a variety of surface molecules on mammalian cells. SA serve as a critical self-recognition molecule in the never-ending warfare with invading pathogens. Many pathogens exploit this feature by scavenging host SA using sialidases, a group of enzymes that catalyze the removal terminal SA from host glycoconjugates. Porphyromonas gingivalis (Pg) is one of the etiological agents of periodontal disease due to its exquisite manipulation of the host immune system to cause chronic inflammation and dysbiosis in the oral cavity. Interestingly, all the genome-sequenced Pg strains have a highly conserved sialidase. Recent studies have shown that sialidase (PG0352) plays a critical role in the pathophysiology of Pg, such as capsule formation, biofilms, and serum complement resistance; however, its underlying molecular mechanism remains largely unknown. The goal of this application is to fill this knowledge gap by focusing on the following aims: Aim 1 seeks to understand the biochemical features of PG0352; Aim 2 is to elucidate the mechanism by which PG0352 protects Pg from the serum complement killing; and Aim 3 is to investigate how Pg acquires SA through studies of a putative novel SA transporter. The findings from this application will provide new insights into understanding the role of SA and sialidase in the pathogenesis of periodontitis. In addition, this multidisciplinary research project will enhance the applicant's knowledge and technical skills in bacterial genetics, protein biochemistry, host-pathogen interactions, immunology and glycobiology.