RESUMO
Corynebacterium species are globally ubiquitous in human nasal microbiota across the lifespan. Moreover, nasal microbiota profiles typified by higher relative abundances of Corynebacterium are often positively associated with health. Among the most common human nasal Corynebacterium species are C. propinquum, C. pseudodiphtheriticum, C. accolens, and C. 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 nasal Corynebacterium strain genomes: 31 from Botswana and 56 from the U.S. C. pseudodiphtheriticum had 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 of C. pseudodiphtheriticum lacked 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.
RESUMO
Dolosigranulum pigrum is positively associated with indicators of health in multiple epidemiological studies of human nasal microbiota. Knowledge of the basic biology of D. pigrum is a prerequisite for evaluating its potential for future therapeutic use; however, such data are very limited. To gain insight into D. pigrum's chromosomal structure, pangenome, and genomic stability, we compared the genomes of 28 D. pigrum strains that were collected across 20 years. Phylogenomic analysis showed closely related strains circulating over this period and closure of 19 genomes revealed highly conserved chromosomal synteny. Gene clusters involved in the mobilome and in defense against mobile genetic elements (MGEs) were enriched in the accessory genome versus the core genome. A systematic analysis for MGEs identified the first candidate D. pigrum prophage and insertion sequence. A systematic analysis for genetic elements that limit the spread of MGEs, including restriction modification (RM), CRISPR-Cas, and deity-named defense systems, revealed strain-level diversity in host defense systems that localized to specific genomic sites, including one RM system hot spot. Analysis of CRISPR spacers pointed to a wealth of MGEs against which D. pigrum defends itself. These results reveal a role for horizontal gene transfer and mobile genetic elements in strain diversification while highlighting that in D. pigrum this occurs within the context of a highly stable chromosomal organization protected by a variety of defense mechanisms. IMPORTANCE Dolosigranulum pigrum is a candidate beneficial bacterium with potential for future therapeutic use. This is based on its positive associations with characteristics of health in multiple studies of human nasal microbiota across the span of human life. For example, high levels of D. pigrum nasal colonization in adults predicts the absence of Staphylococcus aureus nasal colonization. Also, D. pigrum nasal colonization in young children is associated with healthy control groups in studies of middle ear infections. Our analysis of 28 genomes revealed a remarkable stability of D. pigrum strains colonizing people in the United States across a 20-year span. We subsequently identified factors that can influence this stability, including genomic stability, phage predators, the role of MGEs in strain-level variation, and defenses against MGEs. Finally, these D. pigrum strains also lacked predicted virulence factors. Overall, these findings add additional support to the potential for D. pigrum as a therapeutic bacterium.
