AUTHOR=Morales-Olavarría Mauricio , Nuñez-Belmar Josefa , González Dámariz , Vicencio Emiliano , Rivas-Pardo Jaime Andres , Cortez Cristian , Cárdenas Juan P. 

TITLE=Phylogenomic analysis of the Porphyromonas gingivalis - Porphyromonas gulae duo: approaches to the origin of periodontitis

JOURNAL=Frontiers in Microbiology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2023.1226166

DOI=10.3389/fmicb.2023.1226166

ISSN=1664-302X

ABSTRACT=<p><italic>Porphyromonas gingivalis</italic> is an oral human pathogen associated with the onset and progression of periodontitis, a chronic immune-inflammatory disease characterized by the destruction of the teeth-supporting tissue. <italic>P. gingivalis</italic> belongs to the genus <italic>Porphyromonas,</italic> which is characterized by being composed of Gram-negative, asaccharolytic, non-spore-forming, non-motile, obligatory anaerobic species, inhabiting niches such as the oral cavity, urogenital tract, gastrointestinal tract and infected wound from different mammals including humans. Among the <italic>Porphyromonas</italic> genus, <italic>P. gingivalis</italic> stands out for its specificity in colonizing the human oral cavity and its keystone pathogen role in periodontitis pathogenesis. To understand the evolutionary process behind <italic>P. gingivalis</italic> in the context of the <italic>Pophyoromonas</italic> genus, in this study, we performed a comparative genomics study with publicly available <italic>Porphyromonas</italic> genomes, focused on four main objectives: (A) to confirm the phylogenetic position of <italic>P. gingivalis</italic> in the <italic>Porphyromonas</italic> genus by phylogenomic analysis; (B) the definition and comparison of the pangenomes of <italic>P. gingivalis</italic> and its relative <italic>P. gulae</italic>; and (C) the evaluation of the gene family gain/loss events during the divergence of <italic>P. gingivalis</italic> and <italic>P. gulae</italic>; (D) the evaluation of the evolutionary pressure (represented by the calculation of Tajima-D values and dN/dS ratios) comparing gene families of <italic>P. gingivalis</italic> and <italic>P. gulae</italic>. Our analysis found 84 high-quality assemblies representing <italic>P. gingivalis</italic> and 14 <italic>P. gulae</italic> strains (from a total of 233 <italic>Porphyromonas</italic> genomes). Phylogenomic analysis confirmed that <italic>P. gingivalis</italic> and <italic>P. gulae</italic> are highly related lineages, close to <italic>P. loveana</italic>. Both organisms harbored open pangenomes, with a strong core-to-accessory ratio for housekeeping genes and a negative ratio for unknown function genes. Our analyses also characterized the gene set differentiating <italic>P. gulae</italic> from <italic>P. gingivalis</italic>, mainly associated with unknown functions. Relevant virulence factors, such as the FimA, Mfa1, and the hemagglutinins, are conserved in <italic>P. gulae, P. gingivalis,</italic> and <italic>P. loveana</italic>, suggesting that the origin of those factors occurred previous to the <italic>P. gulae</italic> - <italic>P. gingivalis</italic> divergence. These results suggest an unexpected evolutionary relationship between the <italic>P. gulae - P. gingivalis</italic> duo and <italic>P. loveana</italic>, showing more clues about the origin of the role of those organisms in periodontitis.</p>