title: Porphyromonas gingivalis strain specific interactions with human coronary artery endothelial cells: a comparative study.
abstract: Both epidemiologic and experimental findings suggest that infection with Porphyromonas gingivalis exacerbates progression of atherosclerosis. As P. gingivalis exhibits significant strain variation, it is reasonable that different strains possess different capabilities and/or mechanisms by which they promote atherosclerosis. Using P. gingivalis strains that have been previously evaluated in the ApoE null atherosclerosis model, we assessed the ability of W83, A7436, 381, and 33277 to adhere, invade, and persist in human coronary artery endothelial (HCAE) cells. W83 and 381 displayed an equivalent ability to adhere to HCAE cells, which was significantly greater than both A7436 and 33277 (P<0.01). W83, 381, and 33277 were more invasive than A7436 (P<0.0001). However, only W83 and A7436 were able to remain viable up to 48 hours in HCAE cell cultures, whereas 381 was cleared by 48 hours and 33277 was cleared by 24 hours. These differences in persistence were in part due to strain specific differences in intracellular trafficking. Both W83 and 381 trafficked through the autophagic pathway, but not A7436 or 33277. Internalized 381 was the only strain that was dependent upon the autophagic pathway for its survival. Finally, we assessed the efficacy of these strains to activate HCAE cells as defined by production of IL-6, IL-8, IL-12p40, MCP-1, RANTES, TNF-α, and soluble adhesion molecules (sICAM-1, sVCAM-1, and sE-selectin). Only moderate inflammation was observed in cells infected with either W83 or A7436, whereas cells infected with 381 exhibited the most profound inflammation, followed by cells infected with 33277. These results demonstrate that virulence mechanisms among different P. gingivalis strains are varied and that pathogenic mechanisms identified for one strain are not necessarily applicable to other strains.
authors.affiliation: Department of Oral Biology, College of Dentistry and Center for Molecular Microbiology, University of Florida, Gainesville, Florida, United States of America.
authors.forename: Paulo H
authors.initials: PH
authors.lastname: Rodrigues
authors.forename: Leticia
authors.initials: L
authors.lastname: Reyes
authors.forename: Amandeep S
authors.initials: AS
authors.lastname: Chadda
authors.forename: Myriam
authors.initials: M
authors.lastname: Bélanger
authors.forename: Shannon M
authors.initials: SM
authors.lastname: Wallet
authors.forename: Debra
authors.initials: D
authors.lastname: Akin
authors.forename: William
authors.initials: W
authors.lastname: Dunn
authors.forename: Ann
authors.initials: A
authors.lastname: Progulske-Fox
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D050197:Atherosclerosis / Q000382:microbiology; D001422:Bacterial Adhesion; D002470:Cell Survival; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000473:pathology*; D019040:E-Selectin / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D054884:Host-Pathogen Interactions; D006801:Humans; D051907:Lysosomal Membrane Proteins / Q000378:metabolism; D050296:Microbial Viability; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects; D016966:Porphyromonas gingivalis / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D013045:Species Specificity; D014617:Vacuoles / Q000382:microbiology; D052118:Lysosomal-Associated Membrane Protein 1
chemical_list: D000225:Adenine; D019040:E-Selectin; D051907:Lysosomal Membrane Proteins; D008869:Microtubule-Associated Proteins; C489116:LAMP1 protein, human; D052118:Lysosomal-Associated Membrane Protein 1; C477012:MAP1LC3A protein, human; C546936:SELE protein, human; C025946:3-methyladenine