Characterization of a novel microbiome marker anti-correlated with Staphylococcus aureus carriage in the infant nasal microbiome

Staphylococcus aureus carriage in the nasal microbiome is an important determinant of subsequent S. aureus soft tissue infection. Identifying elements of the nasal microbiome that influence carriage provides insight on how to modulate these factors to prevent progression to infection. Prior work by Accorsi et al. 20201 discovered an uncharacterized, taxonomically unassigned ORF that was the major predictor of whether infant microbiome samples evaluated with shotgun metagenomic sequencing contained S. aureus. Subsequent investigation indicated that this ORF was actually a segment of 16S rRNA gene sequence incorrectly annotated by UniProt as a protein-coding gene. In order to determine its true provenance and possible roles in preventing S. aureus carriage, we performed updated taxonomic and functional profiling of 284 shotgun metagenomes from nasal swabs spanning 36 mother-infant pairs monthly for the first year of life. We then analyzed which known gene families were correlated with the marker by 1) performing covariation-based genome reconstruction and 2) traditional metagenomic assembly. Our analyses found that this marker was weakly positively correlated with gene families classified to Streptococcus species and Dolosigranulum pigrum. Our assembly showed larger genomic fragments with portions that annotated as 16S rRNA gene fragments from similar species. We confirmed these findings by using parallel analyses on 267 nares metagenomes from the Expanded Human Microbiome Project. Our analyses thus provide substantial initial support for the hypothesis that this sequence represents a phylogenetic marker for a novel clade with genomic similarity to Streptococcus species and D. pigrum, which could antagonize S. aureus during colonization of the infant nasal microbiome.