Metabolic capabilities are highly conserved among human nasal-associatedCorynebacteriumspecies in pangenomic analyses

Abstract

ABSTRACTCorynebacteriumspecies are globally ubiquitous in human nasal microbiota across the lifespan. Moreover, nasal microbiota profiles typified by higher relative abundances ofCorynebacteriumare often positively associated with health. Among the most common human nasalCorynebacteriumspecies areC. propinquum,C. pseudodiphtheriticum, C. accolens, andC. tuberculostearicum. Based on the prevalence of these species, at least two likely coexist in the nasal microbiota of 82% of adults. To gain insight into the functions of these four species, we identified genomic, phylogenomic, and pangenomic properties and estimated the functional protein repertoire and metabolic capabilities of 87 distinct human nasalCorynebacteriumstrain genomes: 31 from Botswana and 56 from the U.S.C. pseudodiphtheriticumhad geographically distinct clades consistent with localized strain circulation, whereas some strains from the other species had wide geographic distribution across Africa and North America. All four species had similar genomic and pangenomic structures. Gene clusters assigned to all COG metabolic categories were overrepresented in the persistent (core) compared to the accessory genome of each species indicating limited strain-level variability in metabolic capacity. Moreover, core metabolic capabilities were highly conserved among the four species indicating limited species-level metabolic variation. Strikingly, strains in the U.S. clade ofC. pseudodiphtheriticumlacked genes for assimilatory sulfate reduction present in the Botswanan clade and in the other studied species, indicating a recent, geographically related loss of assimilatory sulfate reduction. Overall, the minimal species and strain variability in metabolic capacity implies coexisting strains might have limited ability to occupy distinct metabolic niches.IMPORTANCEPangenomic analysis with estimation of functional capabilities facilitates our understanding of the full biologic diversity of bacterial species. We performed systematic genomic, phylogenomic, and pangenomic analyses with qualitative estimation of the metabolic capabilities of four common human nasalCorynebacteriumspecies generating a foundational resource. The prevalence of each species in human nasal microbiota is consistent with the common coexistence of at least two species. We identified a notably high level of metabolic conservation within and among species indicating limited options for species to occupy distinct metabolic niches and pointing to the importance of investigating interactions among nasalCorynebacteriumspecies. Comparing strains from two continents,C. pseudodiphtheriticumhad restricted geographic strain distribution characterized by an evolutionarily recent loss of assimilatory sulfate reduction in North American strains. Our findings contribute to understanding the functions ofCorynebacteriumwithin human nasal microbiota and to evaluating their potential for future use as biotherapeutics.