Fusobacterium nucleatum secretes amyloid-like FadA to enhance pathogenicity.

Fusobacterium nucleatum (Fn) is a Gram-negative oral commensal, prevalent in various human diseases. It is unknown how this common commensal converts to a rampant pathogen. We report that Fn secretes an adhesin (FadA) with amyloid properties via a Fap2-like autotransporter to enhance its virulence. The extracellular FadA binds Congo Red, Thioflavin-T, and antibodies raised against human amyloid ß42. Fn produces amyloid-like FadA under stress and disease conditions, but not in healthy sites or tissues. It functions as a scaffold for biofilm formation, confers acid tolerance, and mediates Fn binding to host cells. Furthermore, amyloid-like FadA induces periodontal bone loss and promotes CRC progression in mice, with virulence attenuated by amyloid-binding compounds. The uncleaved signal peptide of FadA is required for the formation and stability of mature amyloid FadA fibrils. We propose a model in which hydrophobic signal peptides serve as "hooks" to crosslink neighboring FadA filaments to form a stable amyloid-like structure. Our study provides a potential mechanistic link between periodontal disease and CRC and suggests anti-amyloid therapies as possible interventions for Fn-mediated disease processes.

Association between periodontitis and spontaneous abortion: A case-control study.

BACKGROUND: Spontaneous abortion, or miscarriage, is a complication of pregnancy which can severely affect women both physically and psychologically. We investigated the associations of periodontitis and periodontopathic bacteria with spontaneous abortion. METHODS: We conducted a matched case-control study in two tertiary hospitals in Khon Kaen, Thailand. Cases were 85 women with spontaneous abortion at <20 weeks of gestation matched to 85 controls on age, gestational age, and hospital. Full-mouth periodontal examinations were performed. Periodontitis was defined as at least one site with probing depth ≥5 mm and clinical attachment level ≥2 mm at the same site. Subgingival plaque samples were collected to determine the levels of Porphyromonas gingivalis, Tannerella forsythia, and Fusobacterium nucleatum using real time polymerase chain reaction. RESULTS: The cases were significantly more likely to have periodontitis (50.6%) than the controls (21.2%; P = 0.007). Conditional logistic regression revealed a crude odds ratio (OR) of 4.1 for the association between periodontitis and spontaneous abortion (95% confidence interval [CI] = 1.9-8.9, P = 0.001). The OR decreased, but was still significant, after controlling for previous miscarriage (OR = 3.3, 95% CI = 1.4-7.8, P = 0.006). There was no significant association between the levels of periodontopathic bacteria and spontaneous abortion. Increased levels of P. gingivalis and F. nucleatum were associated with periodontitis in both case and control groups. Association between increased T. forsythia levels and periodontitis was observed only in the case women. CONCLUSIONS: Periodontitis was more common in women with spontaneous abortions as compared with matched controls. Levels of periodontopathic bacteria was not associated with spontaneous abortion in this population.