Porphyromonas gingivalis, the keystone pathogen responsible for dysbiosis in the oral microbiome, the development of periodontal diseases, and the contribution to systemic comorbidities, is a heme auxotroph. It encodes only four enzymes in the heme biosynthesis pathway (HemD, HemN, HemG, and HemH). Comparative genomic analyses demonstrated that, while many Bacteroidota members have lost most of the canonical heme biosynthetic enzymes, Porphyromonas species uniquely retained a ferrochelatase (HemH) homolog. This study aimed to functionally characterize the P. gingivalis HemH protein to prove its hypothesized role in heme formation. HemH can bind heme and PPIX and insert iron or manganese ions into the PPIX ring. The deletion of the hemH gene triggers a heme-starvation response characterized by transcriptional activation of heme uptake systems and virulence-associated genes, coupled with repression of transport and surface proteins preferentially expressed in heme-rich conditions. Therefore, it is proposed that HemH may play a role in maintaining proper heme homeostasis. In a heme-limited environment, P. gingivalis may use intracellular iron and PPIX reserves to synthesize heme by HemH, thereby contributing to heme supply.
Śmiga et al. (Tue,) studied this question.