Affiliation:
1. Groupe de Recherche en Écologie Buccale, Faculté de Médecine Dentaire, Université Laval, Quebec City, Quebec, Canada
Abstract
ABSTRACT
Porphyromonas gingivalis
is a gram-negative anaerobic bacterium that is considered the key etiologic agent of chronic periodontitis. Arg- and Lys-gingipain cysteine proteinases produced by
P. gingivalis
are key virulence factors and are believed to be essential for significant tissue component degradation, leading to host tissue invasion by periodontopathogens. Two in vitro models were used to determine the extent to which
P. gingivalis
can reach connective tissue. The tissue penetration potential of
P. gingivalis
was first investigated by using an engineered human oral mucosa model composed of normal human epithelial cells and fibroblasts. Internalized bacteria were assessed by transmission electron microscopy. Bacteria were observed within multilayered gingival epithelial cells and in the space between the stratified epithelium and the lamina propria. A gingipain-null mutant strain of
P. gingivalis
was found to be less potent in penetrating tissue than the wild-type strain. Proinflammatory responses to
P. gingivalis
infection were evaluated.
P. gingivalis
increased the secretion of interleukin-1β, interleukin-6, interleukin-8, and tumor necrosis factor alpha. In the second part of the study, the contribution of
P. gingivalis
gingipains to tissue penetration was investigated by using a reconstituted basement membrane model (Matrigel). The penetration of
14
C-labeled
P. gingivalis
cells through Matrigel was significantly reduced when leupeptin, a specific inhibitor of Arg-gingipain activity, was added or when a gingipain-null mutant was used. The results obtained with these two relevant models support the capacities of
P. gingivalis
to infiltrate periodontal tissue and to modulate the proinflammatory response and suggest a critical role of gingipains in tissue destruction.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Immunology,Microbiology,Parasitology
Cited by
125 articles.
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