AbstractHeme utilization inPorphyromonas gingivalisrequires 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 ofhmuR,kgpandrgpAgenes in response to growth with different heme sources was examined by reverse transcription-polymerase chain reaction and enzyme-linked immunoassay. Coordinate regulation ofhmuR,kgpandrgpAgene expression was evaluated through utilization ofP. gingivalis hmuRandkgpmutants or by selective inactivation of proteinases with Kgp- and Rgp-specific inhibitors. We observed that expression of thekgpandrgpAgenes was not tightly regulated by heme, but rather by the growth phase. In contrast, expression of thehmuRgene was negatively regulated by heme, while growth ofP. gingivaliswith human serum resulted in increasedhmuRexpression. AP. gingivalis kgpisogenic mutant demonstrated significantly increasedhmuRgene expression, and inactivation of Kgp and Rgp activity by specific inhibitors up-regulatedhmuRgene transcription. Moreover, inactivation of Kgp up-regulatedrgpAtranscription. Finally, aP. gingivalis hmuRmutant exhibited repressedkgpgene expression and lysine-specific proteinase activity. Collectively, these results indicate thatkgp,rgpAandhmuRgene transcription is coordinately regulated and may facilitate greater efficiency of heme utilization inP. gingivalis.