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 (n=284) using shotgun metagenomic sequencing. The infant nasal microbiome was highly variable, particularly within the first 1-2 months. It was weakly influenced by maternal nasal microbiome composition, but primarily shaped by developmental and external factors (e.g. daycare). Infants displayed 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. Furthermore, we identified a gene family, likely acting as a taxonomic marker for an unclassified species, that was significantly anticorrelated with S. aureus in infants and mothers. In gene-content based strain profiling, infant S. aureus strains were more similar to maternal strains. This improved understanding of S. aureus colonization is an important first step toward development of novel, ecological therapies for controlling S. aureus carriage.