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Heme utilization in  Porphyromonas gingivalis  requires the participation of an outer membrane hemin/hemoglobin receptor, HmuR, the lysine-specific gingipain proteinase (Kgp) and arginine-specific gingipain proteinase (Rgp). In this study, the expression of  hmuR ,  kgp  and  rgpA  genes in response to growth with different heme sources was examined by reverse transcription-polymerase chain reaction and enzyme-linked immunoassay. Coordinate regulation of  hmuR ,  kgp  and  rgpA  gene expression was evaluated through utilization of  P. gingivalis hmuR  and  kgp  mutants or by selective inactivation of proteinases with Kgp- and Rgp-specific inhibitors. We observed that expression of the  kgp  and  rgpA  genes was not tightly regulated by heme, but rather by the growth phase. In contrast, expression of the  hmuR  gene was negatively regulated by heme, while growth of  P. gingivalis  with human serum resulted in increased  hmuR  expression. A  P. gingivalis kgp  isogenic mutant demonstrated significantly increased  hmuR  gene expression, and inactivation of Kgp and Rgp activity by specific inhibitors up-regulated  hmuR  gene transcription. Moreover, inactivation of Kgp up-regulated  rgpA  transcription. Finally, a  P. gingivalis hmuR  mutant exhibited repressed  kgp  gene expression and lysine-specific proteinase activity. Collectively, these results indicate that  kgp ,  rgpA  and  hmuR  gene transcription is coordinately regulated and may facilitate greater efficiency of heme utilization in  P. gingivalis .

biological chemistry

Coordinate expression of the  Porphyromonas gingivalis  lysine-specific gingipain proteinase, Kgp, arginine-specific gingipain proteinase, RgpA, and the heme/hemoglobin receptor, HmuR