ABSTRACTResources 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 nasalActinobacteriaandStaphylococcusspp. We found that isolates of coagulase-negative staphylococci (CoNS) were sensitive to growth inhibition byActinobacteriabut thatStaphylococcus aureusisolates were resistant to inhibition. AmongActinobacteria, we observed thatCorynebacteriumspp. were variable in their ability to inhibit CoNS. We sequenced the genomes of 10Corynebacteriumspecies isolates, including 3Corynebacterium propinquumisolates that strongly inhibited CoNS and 7 otherCorynebacteriumspecies isolates that only weakly inhibited CoNS. Using a comparative genomics approach, we found that theC. propinquumgenomes were enriched in genes for iron acquisition and harbored a biosynthetic gene cluster (BGC) for siderophore production, absent in the noninhibitoryCorynebacteriumspecies genomes. Using a chrome azurol S assay, we confirmed thatC. propinquumproduced siderophores. We demonstrated that iron supplementation rescued CoNS from inhibition byC. propinquum, suggesting that inhibition was due to iron restriction through siderophore production. Through comparative metabolomics and molecular networking, we identified the siderophore produced byC. propinquumas dehydroxynocardamine. Finally, we confirmed that the dehydroxynocardamine BGC is expressedin vivoby 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.IMPORTANCEWithin the nasal cavity, interference competition through antimicrobial production is prevalent. For instance, nasalStaphylococcusspecies 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 thatCorynebacterium propinquumproduces 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 expressedin vivo. 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.
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