Individual bacterial taxa drive colonisation resistance to methicillin-resistant Staphylococcus aureus in human nasal microbiome samples

Identifying bacterial interactions that determine susceptibility of human microbiomes to colonisation by pathogenic bacteria has crucial implications for understanding health and disease and, consequently, improving treatment and prevention. Here, we show how microbiome composition of healthy-human nasal passage samples determines susceptibility to colonisation by methicillin-resistant Staphylococcus aureus (MRSA) using a replicated microcosm approach. We find that variable MRSA population growth among samples from different individuals is associated with differences in microbial community composition. To identify individual taxa contributing to in vitro colonisation resistance, we isolate bacteria from inhibitory samples and measure their effects on MRSA in co-culture. This reveals strong MRSA inhibition by multiple Enterobacteriaceae isolates, including some which fully suppress MRSA growth in our system. Finally, by assembling nasal model communities reflecting the composition of natural nasal microbiome samples and combining drop-in and drop-out designs, we show that individual taxa can drive community-level resistance to MRSA growth. Together, our results demonstrate causal links between taxonomic composition of nasal microbiome samples and resistance to S. aureus, informing potential new microbiome-targeted interventions to manage S. aureus colonisation.