Nasal microbiome inhabitants with anti-Staphylococcus aureus activity

Staphylococcus aureus (SA) colonizes most mammals but also represents a danger in clinical settings because it evolves resistance against antibiotics, and SA infections represent a leading cause of death worldwide. SA nasal carriage provides the bacterial reservoir for opportunistic infection because clinical strains often match the patient's own nasally carried strain. The global SA carriage rate is typically reported as 25%-30% after sampling subjects once or twice and defining carrier status using culture-based methods. Here, we collected nasal swabs from 31 healthy subjects twice weekly for an average of 5 months and determined that 23 of 31 subjects (74.9%) presented SA colonies at least once during longitudinal sampling. We explored the nasal microbiota of individuals who rarely or never tested SA-positive and evaluated 25 nasal isolates for anti-SA properties using culture conditions modeling the nasal mucosa. We determined that members of the Gammaproteobacteria class, including Klebsiella spp., Serratia marcescens, and Enterobacter hormaechei, inhibited SA survival. Firmicutes Dolosigranulum pigrum and Streptococcus mitis/oralis also inhibited SA recovery from nasal tissues. Klebsiella spp. (aerogenes, variicola, pneumoniae) activity was contact-independent and not mediated by sequestration of iron or other vital nutrients. K. aerogenes was the most potent SA inhibitor (>99% reduction), and its action was mediated by secreted cationic peptide(s) or protein(s). Collectively, this project determined that most people may be nasally colonized with SA throughout life. It also represents an important step toward explaining why some hosts don't exhibit detectable nasal SA and highlights a potential source of naturally occurring and novel antibiotics targeting SA.

Staphylococcus aureus (SA) is a common member of the human microbiota, colonizing people transiently throughout life, and SA nasal carriage is an important reservoir for the spread of this bacterium. The global economic toll of SA infections is enormous, and antibiotic-resistant strains continue to emerge. Therefore, new approaches to decolonize carriers of SA are urgently needed. To better understand the dynamics of nasal SA carriage versus non-carriage, we monitored subjects longitudinally and isolated and identified species that associate with SA culture-negative noses. While several members of the Gammaproteobacteria class demonstrated anti-SA activity, the nasal Klebsiella spp. potently inhibited (>99%) SA survival in a contact-independent manner. For multiple nasal isolates of K. aerogenes from our donor cohort, this inhibition was attributed to a small, cationic, proteinaceous molecule(s). The secreted products of nasal Gammaproteobacteria (e.g., Klebsiella/Serratia spp.) warrant further investigation as potential sources of new SA decolonization agents.