Competition among Nasal Bacteria Suggests a Role for Siderophore-Mediated Interactions in Shaping the Human Nasal Microbiota.

Resources available in the human nasal cavity are limited. Therefore, to successfully colonize the nasal cavity, bacteria must compete for scarce nutrients. Competition may occur directly through interference (e.g., antibiotics) or indirectly by nutrient sequestration. To investigate the nature of nasal bacterial competition, we performed coculture inhibition assays between nasal and spp. We found that isolates of coagulase-negative staphylococci (CoNS) were sensitive to growth inhibition by but that isolates were resistant to inhibition. Among , we observed that spp. were variable in their ability to inhibit CoNS. We sequenced the genomes of 10 species isolates, including 3 isolates that strongly inhibited CoNS and 7 other species isolates that only weakly inhibited CoNS. Using a comparative genomics approach, we found that the genomes were enriched in genes for iron acquisition and harbored a biosynthetic gene cluster (BGC) for siderophore production, absent in the noninhibitory species genomes. Using a chrome azurol S assay, we confirmed that produced siderophores. We demonstrated that iron supplementation rescued CoNS from inhibition by , suggesting that inhibition was due to iron restriction through siderophore production. Through comparative metabolomics and molecular networking, we identified the siderophore produced by as dehydroxynocardamine. Finally, we confirmed that the dehydroxynocardamine BGC is expressed by analyzing human nasal metatranscriptomes from the NIH Human Microbiome Project. Together, our results suggest that bacteria produce siderophores to compete for limited available iron in the nasal cavity and improve their fitness. Within the nasal cavity, interference competition through antimicrobial production is prevalent. For instance, nasal species strains can inhibit the growth of other bacteria through the production of nonribosomal peptides and ribosomally synthesized and posttranslationally modified peptides. In contrast, bacteria engaging in exploitation competition modify the external environment to prevent competitors from growing, usually by hindering access to or depleting essential nutrients. As the nasal cavity is a nutrient-limited environment, we hypothesized that exploitation competition occurs in this system. We determined that produces an iron-chelating siderophore, and this iron-sequestering molecule correlates with the ability to inhibit the growth of coagulase-negative staphylococci. Furthermore, we found that the genes required for siderophore production are expressed Thus, although siderophore production by bacteria is often considered a virulence trait, our work indicates that bacteria may produce siderophores to compete for limited iron in the human nasal cavity.