Determinants of Staphylococcus aureus carriage in the developing infant nasal microbiome

Staphylococcus aureus is a leading cause of healthcare- and community-associated infections and can be difficult to treat due to antimicrobial resistance. About 30% of individuals carry S. aureus asymptomatically in their nares, a risk factor for later infection, and interactions with other species in the nasal microbiome likely modulate its carriage. It is thus important to identify ecological or functional genetic elements within the maternal or infant nasal microbiomes that influence S. aureus acquisition and retention in early life. We recruited 36 mother-infant pairs and profiled a subset of monthly longitudinal nasal samples from the first year after birth using shotgun metagenomic sequencing. The infant nasal microbiome is highly variable, weakly influenced by maternal nasal microbiome composition, and primarily shaped by developmental and external factors, such as daycare. Infants display distinctive patterns of S. aureus carriage, positively associated with Acinetobacter species, Streptococcus parasanguinis, Streptococcus salivarius, and Veillonella species and inversely associated with maternal Dolosigranulum pigrum. In gene-content based strain profiling, infant S. aureus strains are more similar to maternal strains. Mothers may represent a sporadic early source for S. aureus transmission to the naïve infant microbiome, but microbiome determinants become more important later in the first year. Furthermore, we identified a specific protein family that is highly predictive of infant S. aureus status, significantly anticorrelated with S. aureus positivity in both infants and mothers, sufficiently prevalent to drive widespread patterns of S. aureus carriage, and which ecologically interacts with the commensal species D. pigrum. In subsequent companion work, we determined that this (misannotated) protein family was a non-protein-coding sequence acting as a phylogenetic marker of a likely novel bacterial clade. Our study provides an improved understanding of how the infant nasal microbiome develops in early life, and how it can act to promote or exclude S. aureus colonization.