Host-Bacterial Interactions in Post-treatment Apical Periodontitis: A Metaproteome Analysis

Introduction: This study evaluated the bacterial and human metaproteome of root apexes and the matched inflammatory lesions from teeth with post-treatment apical periodontitis. Methods: Root apexes and matched inflammatory lesions from root canal treated teeth with apical periodontitis were obtained during periradicular surgery. All root canal fillings were rated as adequate on the basis of radiographs and cone beam computed tomography. The specimens were cryopulverized and subjected to metaproteomic analysis for human and bacterial proteins by using a mass spectrometry platform that is based on nanoflow liquid chromatography coupled with linear ion trap quadrupole Velos Orbitrap. Results: The metaproteome analyses revealed the presence of viable and metabolically active human and bacterial cells in both apexes and lesions. Several bacterial proteins of interest for pathogenicity and therapeutics were identified in both apexes and lesions, including proteins related to antibiotic resistance, proteolytic function, stress response, adhesion, and virulence. Many human proteins related to immune defense mechanisms were also detected in both root apex and lesion specimens, including immunoglobulins,, complement system, and proteins linked to T-cell and B-cell activation, neutrophil microbicidal processes, antigen recognition/presentation, bone resorption, and protection against tissue damage. Conclusions: Occurrence of host defense factors from the innate and adaptive immune responses and bacterial virulence, survival, and resistance proteins in matched root apexes/periradicular inflammatory lesions indicates a complex and dynamic host-pathogen interaction in teeth with post-treatment apical periodontitis.