Regulation of Hemin Binding Proteins by a Novel Transcriptional Activator in Porphyromonas gingivalis

Abstract

One of the features of the periodontal pathogen Porphyromonas gingivalis is the presence of complex iron acquisition systems that include an hmuYRSTUV locus. HmuY and HmuR are hemin binding proteins required for P. gingivalis growth. Previous studies have demonstrated that expression of the hmu locus is regulated in response to environmental changes, such as growth phases. However, the mechanisms involved in hmu gene regulation are poorly understood. Here we report that a novel transcriptional activator, PG1237, is required for the expression of humY and humR, but not other iron acquisition-related genes, such as fetB and tlr, which also encode hemin binding proteins. Real-time reverse transcription-PCR analysis revealed that a mutation in the pg1237 gene decreased expression of hmuY and hmuR 149- and 25-fold, respectively, compared to that observed in the wild-type strain. In addition, differential expression of hmuY, hmuR, and the pg1237 gene was found to be quorum-sensing dependent, such that higher expression levels of these genes were observed when P. gingivalis was grown at a lower cell density, such as that seen during the early exponential growth phase. This work demonstrates the involvement of a novel transcriptional activator, PG1237, in expression of the hmu operon in a cell density-dependent fashion.