Virulence mechanisms used in the pathogenesis of periodontal diseases caused by Porphyromonas gingivalis

Abstract

Periodontal diseases are characterized by progressive inflammation that destroys the tooth-supporting tissues, leading to gum bleeding and tooth loss. Porphyromonas gingivalis is considered one of the main etiological agents responsible for the initiation and progression of chronic periodontitis. This gram-negative, anaerobic bacterium is a part of a multi-species oral biofilm. P. gingivalis does not have the full pathway of protoporphyrin IX synthesis, nor does it produce siderophores. Therefore, for survival and proliferation, it requires heme as a source of iron and protoporphyrin IX. In order to obtain heme, P. gingivalis uses a number of mechanisms that affect the ability of this bacterium to initiate a pathological condition. This review presents the current knowledge regarding the best-known and characterized systems involved in heme acquisition by P. gingivalis. We focused on processes occurring in the initial states of infection, where gingipain, hemagglutinins, and hemolysins play a crucial role. The mechanisms encoded by hmu, iht and hus operons, including proteins with hemophore-like properties, as well as TonB-dependent outer membrane receptors are described. We present their function and participation in the progression of the infection. In addition, we describe mechanisms produced by P. gingivalis and other periodontopathogens in synergistic processes promoting the growth and virulence of P. gingivalis. We also describe processes regulating iron and heme homeostasis, including the homolog of the Fur protein, the two-component system HaeSR, as well as the OxyR, SigH, and PgDps proteins.