Porphyromonas gingivalis virulence factors and invasion of cells of the cardiovascular system

Our laboratory is interested in the genes and gene products involved in the interactions between Porphyromonas gingivalis (Pg) and the host. These int eractions may occur in either the periodontal tissues or other non-oral hos t tissues such as those of the cardiovascular system. We have previously re ported the cloning of several genes encoding hemagglutinins, surface protei ns that interact with the host tissues, and are investigating their roles i n the disease process. Primary among these is HagA, a very large protein wi th multiple functional groups that have significant sequence homology to pr otease genes of this species. Preliminary evidence indicates that an avirul ent Salmonella typhimurium strain containing hagA is virulent in mice. Thes e data indicate that HagA may be a key virulence factor of Pg. Additionally , we are investigating the invasion of primary human coronary artery endoth elial cells (HCAEC) by Pg because of the recent epidemiological studies ind icating a correlation between periodontal disease (PD) and coronary heart d isease (CHD). We found that some, but not all, strains of Pg are able to in vade these cells. Scanning electron microsopy of the infected HCAEC demonst rated that the invading organisms initially attached to the host cell surfa ce as aggregates and by a "pedestal"-like structure. By transmission electr onmicroscopy it could be seen that internalized bacteria were present withi n multimembranous compartments localized with rough endoplasmic reticulum. In addition, invasion of the HCAEC by Pg resulted in an increase in the deg radation of long-lived cellular proteins. These data indicate that Pg are p resent within autophagosomes and may use components of the autophagic pathw ay as a means to survive intracellularly. However, Pg presence within autop hagosomes in KB cells could not be observed or detected. It is therefore li kely that Pg uses different invasive mechanisms for different host cells. T his and the role of HagA in invasion is currently being investigated furthe r.