Pervasive integrative and conjugative elements shape Porphyromonas gingivalis gene repertoires

Porphyromonas gingivalis ( Pg ) is an oral pathobiont that contributes to periodontal disease and has been associated with systemic health conditions. Although Pg is recognized as exhibiting extensive strain-level genomic diversity and recombination, the extent to which mobile elements contribute to this variation, and their relevance to its fitness and virulence, remain incompletely understood. Our recent study of the Pg pangenome revealed diverse accessory defense-associated genes, raising the question of whether these are carried by unrecognized mobile genetic elements (MGEs). Integrative and conjugative elements (ICEs) are large autonomous mobile elements that often encode genes for proteins beneficial to their bacterial hosts, including defense systems that protect against phage infection. To date, only one ICE, CTnPg1, has been described in Pg .

Here, we developed a bioinformatic approach integrating ICE prediction and curation, hallmark-gene detection, and genomic-context analysis, to investigate ICEs in Pg . We discovered that ICEs are pervasive in Pg genomes, with >90% of genomes harboring at least one ICE. We found that these elements comprise at least five distinct groups, two of which dominate and frequently co-occur in Pg genomes, inserting into distinct characteristic insertion sites. Using marker-gene analysis of enrichment-culture mini-metagenomes from subjects with periodontal disease we detected representatives of these dominant Pg ICE groups, as well as others, in recent clinical samples. We found that anti-defense and defense genes are common in Pg ICEs, and that these elements commonly encode biosynthetic gene clusters, including for menaquinone synthesis and predicted ribosomally synthesized and post-translationally modified peptides (RiPPs). In contrast to the extensive CRISPR-Cas defense targeting we observed for Pg phages, we detected no exact matches between ICE sequences and Pg CRISPR spacers.

This work establishes that ICEs are pervasive contributors to Pg 's pangenome and unique strain-level gene repertoires. Their distinct cargo profiles suggest that ICEs likely impact the virulence and ecology of Pg through the introduction and spread of advantageous traits, including expansion of Pg 's biosynthetic capacity and resistance to phage infection. This work provides a curated framework for investigating ICE diversity in Pg and establishes a foundation for expanded experimental studies of their host ranges and roles in shaping Pg 's interactions with phages, other microbes, and the human host.