The survival status of <i>Porphyromonas gingivalis</i> under low heme conditions

Background Porphyromonas gingivalis (P. gingivalis) is a key pathogen in the initiation and progression of chronic periodontitis. As a heme auxotrophic bacterium, P. gingivalis must acquire heme from the host environment as a source of both iron and the porphyrin ring. The scarcity of heme in healthy periodontal tissues and during the early stages of periodontitis serves as a critical factor governing the viability and pathogenic potential of P. gingivalis. The unique heme uptake pathway supports targeted treatment development.Objective This review systematically summarizes the adaptive mechanisms of P. gingivalis in nutrient-restricted environments, its crosstalk with oral microbes, and related therapeutic strategies.Design We review the published literature and elucidate the survival mechanisms of P. gingivalis in nutrient-restricted environments from five dimensions: growth morphology, virulence phenotype, heme transport system, metabolic enzyme activity, and transcriptional regulatory network. We also explore the possible mechanisms by which P. gingivalis disrupts immune homeostasis, leading to microbial dysbiosis, and analyze its synergistic interactions with other oral microorganisms. Based on the unique heme acquisition mechanism of P. gingivalis, we summary novel therapeutic strategies reported in existing research.Results Heme limitation reshapes P. gingivalis morphology, virulence, metabolism and heme acquisition systems. Interactions with S. gordonii and C. albicans boost its pathogenicity and trigger microbial dysbiosis. Porphyrin-conjugated antibiotics, antimicrobial photodynamic therapy and vaccines are promising heme-targeted therapies.Conclusions Heme scarcity is a decisive environmental factor regulating the survival and pathogenic transformation of P. gingivalis. Under heme-limited conditions, the bacterium activates a complete set of adaptive survival programs and interacts with other oral microbes to disrupt tissue immune balance and trigger microbial dysbiosis. Targeting its distinctive heme acquisition system is a feasible and promising direction for developing novel therapies against chronic periodontitis.