Metabolic capabilities are highly conserved among human nasal-associatedCorynebacteriumspecies in pangenomic analyses
Authors: Tran Tommy H. , Escapa Isabel F. , Roberts Ari Q. , Gao Wei , Obawemimo Abiola C. , Segre Julia A. , Kong Heidi H. , Conlan Sean , Kelly Matthew S. , Lemon Katherine P. 
Published: June 2023

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. To gain insight into the functions of these four species, we identified genomic, phylogenomic, and pangenomic properties and estimated the metabolic capabilities of 87 distinct human nasalCorynebacteriumstrain genomes: 31 from Botswana and 56 from the USA.C. pseudodiphtheriticumhad geographically distinct clades consistent with localized strain circulation, whereas some strains from the other species had wide geographic distribution spanning Africa and North America. All species had similar genomic and pangenomic structures. Gene clusters assigned to all COG metabolic categories were overrepresented in the persistent versus accessory genome of each species indicating limited strain-level variability in metabolic capacity. Based on prevalence data, at least twoCorynebacteriumspecies likely coexist in the nasal microbiota of 82% of adults. So, it was surprising that core metabolic capabilities were highly conserved among the four species indicating limited species-level metabolic variation. Strikingly, strains in the USA clade ofC. pseudodiphtheriticumlacked genes for assimilatory sulfate reduction present in most of the strains in the Botswana 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, along with focused experimental validations, 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, highlighting 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 USA strains. Our findings contribute to understanding the functions ofCorynebacteriumwithin human nasal microbiota and to evaluating their potential for future use as biotherapeutics.