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Appl Environ Microbiol. 2018 Dec 21. pii: AEM.02406-18. doi: 10.1128/AEM.02406-18. [Epub ahead of print]

Competition among nasal bacteria suggests a role for siderophore-mediated interactions in shaping the human nasal microbiota.

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Department of Bacteriology, University of Wisconsin-Madison, Madison, WI 53706
Department of Bacteriology, University of Wisconsin-Madison, Madison, WI 53706.
Laboratory of Genetics, University of Wisconsin-Madison, Madison, WI 53706.
Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792.
Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792.


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 co-culture inhibition assays between nasal Actinobacteria and Staphylococcus spp. We found that coagulase-negative staphylococci (CoNS) isolates were sensitive to growth inhibition by Actinobacteria but Staphylococcus aureus isolates were resistant to inhibition. Among Actinobacteria, we observed that Corynebacterium spp. were variable in their ability to inhibit CoNS. We sequenced the genomes of ten Corynebacterium spp. isolates, including three Corynebacterium propinquum that strongly inhibited CoNS and seven other Corynebacterium spp. isolates that only weakly inhibited CoNS Using a comparative genomics approach, we found that the C. propinquum genomes were enriched in genes for iron acquisition and encoded a biosynthetic gene cluster (BGC) for siderophore production, absent in the non-inhibitory Corynebacterium spp. genomes. Using a chromeazurol S assay, we confirmed that C. propinquum produced siderophores. We demonstrated that iron supplementation rescued CoNS from inhibition by C. propinquum, suggesting that inhibition was due to iron restriction through siderophore production. Through comparative metabolomics and molecular networking, we identified the siderophore produced by C. propinquum as dehydroxynocardamine. Finally, we confirmed that the dehydroxynocardamine BGC is expressed in vivo 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.IMPORTANCE Within the nasal cavity, interference competition through antimicrobial production is prevalent. For instance, nasal Staphylococcus spp. strains can inhibit the growth of other bacteria through the production of nonribosomal peptides and ribosomally synthesized and post-translationally modified peptides. In contrast, bacteria engaging in exploitation competition modify the external environment to prevent competitors from growing, usually by depleting access to essential nutrients. As the nasal cavity is a nutrient limited environment, we hypothesized that exploitation competition occurs in this system. We determined that Corynebacterium propinquum produces an iron-chelating siderophore and this iron-sequestering molecule correlates with the ability to inhibit the growth of coagulase-negative staphylococci. Further, we found that the genes required for siderophore production are expressed in vivo Thus, though 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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