Zalis, E. A. | bioRxiv Science

bioRxiv2026

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

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.

microbiology↗

bioRxiv2020

Negative interplay between biofilm formation and competence in the environmental strains of Bacillus subtilis

Environmental strains of the soil bacterium Bacillus subtilis have valuable applications in agriculture, industry, and biotechnology. They are capable of forming robust biofilms and demonstrate excellent biological control activities in plant protection. However, environmental strains are genetically less accessible, a sharp contrast to the laboratory strains well known for their natural competence and a limitation toward their application. In this study, we observed that robust biofilm formation of the environmental strains greatly reduces the rate of competent cells within the biofilm. By using the model strain 3610, we reveal a cross-pathway regulation that allows biofilm matrix producers and competence-developing cells to undergo mutually exclusive cell differentiation. We show that the competence activator ComK represses the key biofilm regulatory gene sinI by directly binding to the sinI promoter, thus blocking competent cells from simultaneously becoming matrix producers. In parallel, the biofilm activator SlrR represses competence through three distinct mechanisms, involving both genetic regulation and cell morphological changes. We discuss potential implications of limiting competence in a bacterial biofilm. ImportanceThe soil bacterium Bacillus subtilis is capable of forming robust biofilms, a multicellular community important for its survival in the environment. B. subtilis also exhibits natural competence, the ability of cells to acquire genetic materials directly from the environment. By investigating competence development in situ during B. subtilis biofilm formation, we reveal that robust biofilm formation, an important feature of the environmental strains of B. subtilis, often greatly reduces the rate of competent cells within the biofilm. We characterize a cross-pathway regulation that allows cells associated with these two developmental events to undergo mutually exclusive cell differentiation during biofilm formation. Finally, we discuss potential biological implications of limiting competence in a bacterial biofilm.

microbiology↗