Fusobacterial species: differential sensitivity to human beta defensins

Human beta defensins (hBDs) are epithelial cell derived antimicrobial and immunomodulatory peptides. We previously showed that Fusobacterium nucleatum (Fn), a ubiquitous gram negative bacterium of the oral cavity, induces hBD-2 and -3 expression in human oral epithelial cells and is resistant to them. Objective: To test a number of Fn strains and other fusobacterial species for their sensitivities to recombinant hBD2 and -3, respectively. Methods: Eight Fn strains and representative strains of 5 other fusobacterial species from the oral cavity, pregnant uterus, skin and vagina were tested for susceptibility to hBD-2 and hBD-3. Minimum inhibitory concentration assays were performed by respective incubations with increasing micromolar concentrations of rhBD-2 and rhBD-3. Mixtures were kept at 37º C anaerobically for three hours before serial dilutions and plating. Results: Various degrees of resistance to rhBD-2/ -3 were found. Some demonstrated sensitivity at low concentrations of hBDs (2.5 μg/ml), others were found to be sensitive at higher concentrations of hBDs (5 μg/ml) and still others were totally resistant even at the highest concentrations (10 μg/ml). The overall trend suggests that oral and intrauterine isolates are resistant to rhBD-2, while vaginal and skin isolates are sensitive. All strains tested were more susceptible to rhBD-3 than to rhBD-2, although the degrees of sensitivity varied. Conclusion: Further studies are necessary to determine if the differences in sensitivities to hBDs correlate with the organisms' ability to induce them in epithelial cells and if these properties benefit the host in some sites, while being pathogenic in others. Supported by NIH/NIDCR 1 R01 DE16334 (AW); 1 R01 DE14924 (YWH)