Invasion Strategies of the Oral Pathogen <i>Porphyromonas gingivalis:</i> Implications for Cardiovascular Disease

Abstract

Microorganisms have evolved a variety of mechanisms designed to evade detection and/or destruction by the host. Many pathogens evade host defenses by invading cells, thus providing the bacterium with an environment free of competing microorganisms. Adherence and invasion are active processes in which microorganisms often use host proteins and enzymes to gain entry into the cell, thus stimulating their own uptake. The investigation of invasion by the periopathogen Porphyromonas gingivalis is in its infancy in comparison with that of the enteric pathogens. However, recent studies with P. gingivalis have revealed that these organisms have developed invasion strategies and mechanisms similar to those of the enteric pathogens for both epithelial and endothelial cells. The study and elucidation of the mechanisms by which microorganisms such as P. gingivalis persist in chronic infection will provide valuable insight into the pathogenesis of P. gingivalis-mediated periodontal disease. The ability to multiply in and to activate endothelial cells may be one of the pathogenic mechanisms exerted by P. gingivalis that may explain the recently described association between this organism and cardiovascular disease.

Oral Infection With a Periodontal Pathogen Accelerates Early Atherosclerosis in Apolipoprotein E–Null Mice

“…Evidence for definitive molecular mechanisms underlying these observations are being uncovered, as studies in vitro suggest that P gingivalis can invade primary cultures of human coronary artery endothelial cells. 34,35 These observations suggest that once these bacteria adhere to and invade endothelial cells, they may directly activate signal transduction pathways linked to the proinflammatory response.…”

“…It is important to emphasize again, however, that evidence linking P gingivalis specifically to vascular/inflammatory cell perturbation is already emerging. [32][33][34][35][36] Pilot studies from our group have shown that P gingivalis infection of human monocytes incubated with LDL significantly increased foam cell formation compared with LDL incubation alone. DPG3, the fimbriae-deficient mutant of P gingivalis that lacks the ability to adhere to and invade host cells, an important determinant of its pathogenicity in human periodontitis, did not have such an effect.…”

Autophagy: A Highway for Porphyromonas gingivalis in Endothelial Cells

“…18,21,[43][44][45] In gingival epithelial cells (GEC), P. gingivalis accumulates in the perinuclear area and neither apoptosis nor necrotic cell death is observed. 43,46,47 However, in KB cells the bacteria are found free in the cytosol or within single-membrane bound vacuoles.…”

Is Porphyromonas gingivalis Cell Invasion Required for Atherogenesis? Pharmacotherapeutic Implications

“…These inflammatory molecules have demonstrated significant roles in the initiation and/or acceleration of atherosclerosis. Recent studies have established that P. gingivalis invasion of endothelial cells from various tissues (fetal bovine heart, bovine aorta, and human umbilical vein) is dependent on bacterial fimbriae, as is activation of endothelial responses (9,(33)(34)(35). Furthermore, adherence and invasion of the corresponding FimA mutant DPG3, which lacks the major fimbriae, were not detected (9, 33).…”