OxyR Activation in Porphyromonas gingivalis in Response to a Hemin-Limited Environment

Porphyromonas gingivalis is a Gram-negative obligately anaerobic bacterium associated with several forms of periodontal disease, most closely with chronic periodontitis. Previous studies demonstrated that OxyR plays an important role in the aerotolerance of P. gingivalis by upregulating the expression of oxidative-stress genes. Increases in oxygen tension and in H2O2 both induce activation of OxyR. It is also known that P. gingivalis requires hemin as an iron source for its growth. In this study, we found that a hemin-limited growth environment significantly enhanced OxyR activity in P. gingivalis. As a result, expression of sod, dps, and ahpC was also upregulated. Using a chromatin immunoprecipitation quantitative PCR (qPCR) analysis, DNA binding of activated OxyR to the promoter of the sod gene was enhanced in P. gingivalis grown under hemin-limited conditions compared to excess-hemin conditions. Cellular tolerance of H2O2 was also enhanced when hemin was limited in the growth medium of P. gingivalis. Our work supports a model in which hemin serves as a signal for the regulation of OxyR activity and indicates that P. gingivalis coordinately regulates expression of oxidative-stress-related genes by this hemin concentration-dependent pathway.