Systematic discovery of a topical bacterial consortium that targets Staphylococcus aureus to treat atopic dermatitis

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. Competing Interest Statement C.M.A.A., J.K., and B.C. are co-founders of and have equity interest in Concerto Biosciences. E.L.B., K.A., A.H., O.S., H.A.A., E.Z., A.L., D.C., and K.D.L. are current or past employees of Concerto Biosciences. P.L. reports being on the speaker's bureau for AbbVie, Arcutis, Eli Lilly, Galderma, Incyte, La Roche-Posay/L'Oreal, Pfizer, Pierre-Fabre Dermatologie, Regeneron/Sanofi Genzyme, Verrica; reports on consulting/advisory boards for Alphyn Biologics, AbbVie, Almirall, Amyris, Apogee, Arcutis, Astria Therapeutics, Castle Biosciences, Codex Labs, Concerto Biosciences, Dermavant, Eli Lilly, Galderma, Kenvue, LEO Pharma, Lipidor, L'Oreal, Merck, Micreos, MyOR Diagnostics, Nektar Therapeutics, Nia Health, Pelthos Therapeutics, Novartis, Phyla, Regeneron/Sanofi Genzyme, Sibel Health, Skinfix, Song Lab Skincare, Soteri Skin, Stratum Biosciences, Sun Pharma, Theraplex, Thimble Health, Topaz Biosciences, Unilever, Verdant Scientific, Verrica, Yobee Care. P.L. reports stock options with Akeyna, Inc., Alphyn Labs, Codex Labs, Concerto Biosciences, Song Lab Skincare, Soteri Skin, Stratum Biosciences, Thimble, Topaz Biosciences, Yobee Care, Verdant Scientific. In addition, P.L. has a patent pending for a Theraplex product with royalties paid and is a Scientific Advisory Committee Member emeritus of the National Eczema Association.