Nasal commensals reduceStaphylococcus aureusproliferation by restricting siderophore availability

Abstract

BackgroundThe human microbiome is critically associated with human health and disease. One aspect of this is that antibiotic-resistant opportunistic bacterial pathogens such as methicillin-resistantStaphylococcus aureuscan reside within the nasal microbiota which increases the risk of infections. Epidemiological studies of the nasal microbiome have revealed positive and negative correlations between non-pathogenic species andS. aureus, but the underlying molecular mechanisms remain poorly understood. The nasal cavity is iron-limited and bacteria are known to produce iron-scavenging siderophores to proliferate in such environments. Siderophores are public goods that can be consumed by all members of a bacterial community. Accordingly, siderophores are known to mediate bacterial competition and collaboration but their role in the nasal microbiome is unknown.ResultsHere we show that siderophore acquisition is crucial forS. aureusnasal colonizationin vivo. We screened 94 nasal bacterial strains from seven genera for their capacity to produce siderophores as well as to consume the siderophores produced byS. aureus.We found that 80% of the strains engaged in siderophoremediated interactions withS. aureus.Non-pathogenic corynebacterial species were found to be prominent consumers ofS. aureussiderophores. In co-culture experiments, consumption of siderophores by competitors reducedS. aureusgrowth in an iron-dependent fashion.ConclusionsOur data show a wide network of siderophore mediated interactions between the species of the human nasal microbiome and provide mechanistic evidence for inter-species competition and collaboration impacting pathogen proliferation. This opens avenues for designing nasal probiotics to displaceS. aureusfrom the nasal cavity of humans.