Exploring heme and iron acquisition strategies of Porphyromonas gingivalis-current facts and hypotheses

Iron and heme are crucial for pathogenic bacteria living in the human host but are not available in free form due to their binding by iron- and heme-sequestering proteins. Porphyromonas gingivalis causes dysbiosis in the oral microbiome and is considered a keystone pathogen in the onset and progression of periodontal diseases. Its ability to infect and multiply in host cells and its presence in distant tissues and fluids highlights its pathogenic versatility and explains the relationship between periodontal diseases and systemic or neurodegenerative diseases. Porphyromonas gingivalis has evolved specialized mechanisms that allow it to thrive in the host under adverse nutrient-limited conditions. This review presents the updated summary of the mechanisms of iron and heme acquisition by P. gingivalis, with a central role played by gingipains and the unique Hmu system. The potential role of other iron and heme acquisition systems, such as Hus and Iht, indicates the importance of the partially conserved heme biosynthesis pathway, involving homologs of the HemN, HemG, and HemH proteins. In light of increasing antibiotic resistance, difficulties with diagnosis, and drug administration, targeting the mechanisms of heme and iron acquisition of P. gingivalis represents a promising target for developing diagnostic tests, preventive or therapeutic strategies.