189 Microbial expression of lantibiotics may explain discrepancies between S. aureus culturability and metagenomics in atopic dermatitis subjects and healthy controls

Atopic Dermatitis (AD) is an inflammatory skin disease exacerbated by Staphyloccocus aureus (S. aureus) skin colonization. The Atopic Dermatitis Research Network performed taxonomic analysis of skin swabs from 20 disease severity-matched AD S. aureus culture+ (n=10) and AD culture- (n=10) and 9 culture-, nonatopic (NA) subjects. Metagenomic analysis revealed discrepancies between molecular and culture evidence of S. aureus, suggesting that S. aureus skin burden may not be fully reflected by culture results. We hypothesized that production of lantibiotics by cutaneous microbes, which inhibit S. aureus growth, may explain high genomic S. aureus abundance in culture- samples and vice versa. Since each lantibiotic class (I, II, III & IV) has specific biosynthesis genes (lanB/C, lanM, labKC & lanL, respectively), Hidden Markov Models, previously used to assess oral and stool samples, were used to search metagenomes for these genes. We observed 190 total hits (AD [nonlesional & lesional]: 122, median 1/sample; NA: 68, median 7/sample). Significantly fewer lantibiotic hits were found in S. aureus culture+ AD nonlesional than their metagenomic counterparts (P<0.01) but no difference in lesional samples. BLAST search of peptide sequences revealed 17.0% of lantibiotic hits were from Malassezia restricta, 8.9% from coagulase-negative Staph, 8.9% from Cutibacterium acnes and 7.9% from Malassezia globosa. Our findings suggest that expression of lantibiotics may reduce S. aureus viability and highlights the potential importance of bacterial-fungal dynamics in the skin ecosystem.