Systematic discovery of a topical bacterial consortium that targets Staphylococcus aureus to treat atopic dermatitis
Bean, E. L.; Cervantes, B.; Armentrout, K.; Hassaballah, A. H.; Solebo, O.; Arjes, H. A.; Zalis, E. A.; Lyons, A.; Chin, D.; Lio, P.; Litcofsky, K. D.; Ackerman Araromi, C. M.; Kehe, J.
Show abstract
Atopic dermatitis (AD) flares are frequently accompanied by Staphylococcus aureus overgrowth and activation of quorum sensing-regulated virulence pathways that amplify inflammation and barrier dysfunction. Because commensal members of the skin microbiome can inhibit S. aureus colonization and virulence, we hypothesized that a consortium sourced from healthy human skin could therapeutically target S. aureus and ameliorate AD. We curated 180 skin-derived bacterial strains and used kChip, an ultrahigh-throughput coculture platform, to profile S. aureus physiological response to over four million combinations consisting of two, three, or seven cocultured strains. This screening identified Ensemble No.2 (ENS-002), a three-strain consortium that strongly suppressed S. aureus growth and virulence in follow-up microtiter assays and a Reconstructed Human Epidermis S. aureus Activity (RHESA) model. ENS-002 is now undergoing development as a topical live biotherapeutic product (LBP) treatment for AD.
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