Selective bacterial proteolysis in periodontal disease: Molecular mechanisms and therapeutic implications, a narrative review

Background/Objective: Periodontal diseases are characterized by complex interactions between the immune system, oral bacteria, host tissues, and various external and internal factors. A hallmark of disease progression is the selective degradation of host proteins by bacterial proteases. This review explores the molecular mechanisms of bacterial proteolysis, with a focus on the selectivity toward host proteins essential for oral homeostasis. Methods: An extensive electronic search was conducted using PubMed, Scopus, and Web of Science, covering the last 20 years. Search terms included “degradation,” “oral tissue,” “proteins,” “bacteria,” “periodontal disease,” “periodontitis,” “pathways,” and “host.” Boolean operators and filters were applied to refine results. Articles were evaluated based on titles, abstracts, and full texts. Additional references were identified through citation tracking. A narrative synthesis approach was used to integrate findings. Results: Bacterial proteases exhibit precise substrate recognition, targeting specific structural, immune, and signaling proteins in the oral environment. The proteolytic profile and disease pathology are shaped by microbial community dynamics, including cooperative and competitive interactions. Host factors such as genetic diversity, local microenvironmental conditions, and immune responses further modulate protein degradation. Despite advancements, critical gaps remain, particularly regarding post-translational modifications and the determinants of proteolytic specificity. Conclusions: Selective bacterial proteolysis plays a pivotal role in periodontal disease pathogenesis. Addressing current knowledge gaps through advanced proteomics, longitudinal studies, and imaging technologies is essential for developing targeted diagnostic and therapeutic strategies. An integrative approach is needed to enhance periodontal disease management and improve patient outcomes.