Identification of Nasal Gammaproteobacteria with Potent Activity against Staphylococcus aureus: Novel Insights into the 'Noncarrier' State

Nasal carriage of Staphylococcus aureus is a risk factor for infection, but it is not yet understood why some individuals carry nasal S. aureus persistently, intermittently, or seemingly not at all when tested via culture methods. This study compared the nasal microbiomes of established S. aureus carriers and noncarriers, identified species associated with noncarriage, and tested them for anti-S. aureus activity using assays developed to model the nutrient-limited nasal mucosa.
Staphylococcus aureus nasal carriage provides the bacterial reservoir for opportunistic infection. In comparing the nasal microbiomes of culture-defined persistent S. aureus carriers versus noncarriers, we detected S. aureus DNA in all noses, including those with an established history of S. aureus negativity based on culture. Colonization with Gammaproteobacteria, including Klebsiella aerogenes, Citrobacter koseri, Moraxella lincolnii, and select Acinetobacter spp., was associated with S. aureus noncarriage. We next developed physiological competition assays for testing anti-S. aureus activity of isolated nasal species, utilizing medium modeling the nutrient-limited fluid of the nasal mucosa, polarized primary nasal epithelia, and nasal secretions. K. aerogenes from the nose of an S. aureus noncarrier demonstrated >99% inhibition of S. aureus recovery in all assays, even when S. aureus was coincubated in 9-fold excess. Secreted S. aureus inhibitory proteins from K. aerogenes and M. lincolnii were heat-stable and