Spatial ecology of Haemophilus and Aggregatibacter in the human oral cavity

Abstract

Haemophilus and Aggregatibacter are two of the most common bacterial genera in the human oral cavity, encompassing both commensals and pathogens of substantial ecological and medical significance. In this study, we conducted a metapangenomic analysis of oral Haemophilus and Aggregatibacter species to uncover genomic diversity, phylogenetic relationships, and habitat specialization within the human oral cavity. Using three metrics—pangenomic gene content, phylogenomics, and average nucleotide identity (ANI)—we first identified distinct species and sub-species groups among these genera. Mapping of metagenomic reads then revealed clear patterns of habitat specialization, such as Aggregatibacter species predominantly in dental plaque, a distinctive Haemophilus parainfluenzae sub-species group on the tongue dorsum, and H. sp. HMT-036 predominantly in keratinized gingiva and buccal mucosa. In addition, we found that supragingival plaque samples contained predominantly only one out of the three taxa, H. parainfluenzae, Aggregatibacter aphrophilus, and A. sp. HMT-458, suggesting independent niches or a competitive relationship. Functional analyses revealed the presence of key metabolic genes, such as oxaloacetate decarboxylase, correlated with habitat specialization, suggesting metabolic versatility as a driving force. Additionally, heme synthesis distinguishes H. sp. HMT-036 from closely related Haemophilus haemolyticus, suggesting that the availability of micronutrients, particularly iron, was important in the evolutionary ecology of these species. Overall, our study exemplifies the power of metapangenomics to identify factors that may affect ecological interactions within microbial communities, including genomic diversity, habitat specialization, and metabolic versatility.