title: Tobacco-induced alterations to Porphyromonas gingivalis-host interactions.
abstract: Smokers are more susceptible than non-smokers to persistent infection by Porphyromonas gingivalis, a causative agent of periodontitis. Patients who smoke exhibit increased susceptibility to periodontitis and are more likely to display severe disease and be refractory to treatment. Paradoxically, smokers demonstrate reduced clinical inflammation. We show that P. gingivalis cells exposed to cigarette smoke extract (CSE) induce a lower proinflammatory response (tumour necrosis factor-alpha, interleukin-6, interleukin-12 p40) from monocytes and peripheral blood mononuclear cells than do unexposed bacteria. This effect is reversed when CSE-exposed bacteria are subcultured in fresh medium without CSE. Using microarrays representative of the P. gingivalis genome, CSE-exposure resulted in differential regulation of 6.8% of P. gingivalis genes, including detoxification and oxidative stress-related genes; DNA repair genes; and multiple genes related to P. gingivalis virulence, including genes in the major fimbrial and capsular operons. Exposure to CSE also altered the expression of outer membrane proteins, most notably by inducing the virulence factors RagA and RagB, and a putative lipoprotein cotranscribed with the minor fimbrial antigen. Therefore, CSE represents an environmental stress to which P. gingivalis adapts by altering gene expression and outer membrane proteins. These changes may explain, in part, the altered virulence and host-pathogen interactions that have been documented in vivo in smokers with periodontal disease.
authors.affiliation: Microbiology and Immunology, University of Louisville, Louisville, KY 40292, USA.
authors.forename: Juhi
authors.initials: J
authors.lastname: Bagaitkar
authors.forename: Lisa R
authors.initials: LR
authors.lastname: Williams
authors.forename: Diane E
authors.initials: DE
authors.lastname: Renaud
authors.forename: Manjunatha R
authors.initials: MR
authors.lastname: Bemakanakere
authors.forename: Mike
authors.initials: M
authors.lastname: Martin
authors.forename: David A
authors.initials: DA
authors.lastname: Scott
authors.forename: Donald R
authors.initials: DR
authors.lastname: Demuth
mesh_terms: D002460:Cell Line; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D006790:Host-Parasite Interactions / Q000187:drug effects* / Q000276:immunology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000382:microbiology; D009000:Monocytes / Q000276:immunology / Q000382:microbiology; D016966:Porphyromonas gingivalis / Q000187:drug effects* / Q000276:immunology*; D012907:Smoking; D013312:Stress, Physiological
chemical_list: D016207:Cytokines