Biology subjects

Kehe, J.

Publications and source records attributed to Kehe, J..

3 recordsLinked to original sources

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

Positive interactions are common among culturable bacteria

Interspecies interactions shape the structure and function of microbial communities. In particular, positive, growth-promoting interactions can significantly affect the diversity and productivity of natural and engineered communities. However, the prevalence of positive interactions and the conditions in which they occur are not well understood. To address this knowledge gap, we used kChip, an ultra-high throughput coculture platform, to measure 180,408 interactions among 20 soil bacteria across 40 carbon environments. We find that positive interactions, often described to be rare, occur commonly, primarily as parasitisms between strains that differ in their carbon consumption profiles. Notably, non-growing strains are almost always promoted by strongly growing strains (85%), suggesting a simple positive interaction-mediated approach for cultivation, microbiome engineering, and microbial consortium design. One Sentence SummaryExperimental measurement of >150,000 bacterial cocultures reveals that growth-promoting interactions occur commonly and depend on differences in nutrient consumption preferences.

ecology↗

bioRxiv2017

Combinatorial Drug Discovery in Nanoliter Droplets

Combinatorial drug treatment strategies perturb biological networks synergistically to achieve therapeutic effects and represent major opportunities to develop advanced treatments across a variety of human disease areas. However, the discovery of new combinatorial treatments is challenged by the sheer scale of combinatorial chemical space. Here we report a high-throughput system for nanoliter-scale phenotypic screening that stabilizes a chemical library in nanoliter droplet emulsions and automates the formulation of chemical combinations en mass using parallel droplet processing. We apply this system to predict synergy between more than 4,000 investigational and approved drugs and a panel of 10 antibiotics against E. coli, a model Gram-negative pathogen. We found a range of drugs not previously indicated for infectious disease that synergize with antibiotics. Our validated hits include drugs that synergize with the antibiotics vancomycin, erythromycin, and novobiocin, which are used against Gram-positive bacteria but are not effective by themselves to resolve Gram-negative infections.

bioengineering↗