Abstract
Periodontopathic bacteria produce high concentrations of short-chain fatty acids (SCFAs) in their culture supernatant. Periodontopathic bacteria-produced butyric acid is an extracelluar metabolite that induces apoptosis in neutrophiles, T-cells and macrophages, and it has immunomodulatory properties and facilitates microbial transition in dental plaque. AIDS progression is associated with the development of severe periodontitis. One of our main objectives was to examine whether periodontopathic-bacteria infection facilitates viral progression by reactivating latent viral infections, such as HIV-1 and EBV. With regard to HIV-1, hyperacetylation of histone proteins by histone deacetylase (HDACs) is involved in maintenance of HIV-1 latency repressing HIV-1 proviral DNA-tanscription. We demonstrated that P. gingivalis-culture supernatant, containing butyric acid, acts as potent HDAC inhibitor, appearing to induce histone acetylation which eventually leads to HIV reactivation in latently infected cells. With regard to EBV, the EBV BZLF1 gene product, ZEBRA, is a master regulator in the transition from latency to the lytic replication cycle in latently infected B cells. We also demonstrated that P. gingivalis-culture supernatant inhibited HDACs, thus, increasing histone acetylation and BZLF1 transcriptional activity. Overall, our results suggest that periodontal disease may act as a risk factor in viral infectious disease reactivation in latently infected individuals. Moreover, these findings suggest that butyric acid-producing intestinal bacteria may be involved in the aggravation of viral infections. More importantly, these findings indicate the importance of studying metabolic by-products, such as SCFAs, that may affect microbial interactions, to help elucidate endogenous infection mechanisms.
