Biological sciences will host Dr. Gautam Dantas, Conan Professor of Laboratory and Genomic Medicine at Washington University's School of Medicine, as a guest speaker.

Antibiotics can acutely and persistently compromise microbiome stability and resilience, enabling enhanced colonization of pathogenic microbes, and loss of host-beneficial functions from depleted commensals. Antibiotics also selectively enrich resistance genotypes in interconnected microbiomes. We apply high-throughput functional metagenomic selections for culture-independent characterization of resistomes encoded by the microbiota of humans, animals, soils, and built-environments. We complement these analyses with community taxonomic and functional profiling through whole metagenome shotgun sequencing, and isolate phenotyping and whole genome sequencing. We use these datasets to model and predict the impact of various biotic and abiotic perturbations on the transmission and evolutionary dynamics of diverse microbiomes and their resistomes across time and habitats, through application of generalized linear mixed models and machine learning algorithms. Hundreds of resistance genes we identify from specific taxa in environmental and commensal microbiomes are identical to resistance genes found in major human pathogens, indicating recent genetic exchange between these microbes. We also find thousands of functionally validated resistance genes which are genetically novel, but flanked by genes involved in horizontal gene transfer, including transposases and integrases. Our genetic, biochemical, and structural analyses of some of these novel environmental resistance enzymes have revealed that they are emerging in pathogens, can destroy latest-generation antibiotics (sometimes preceding clinical deployment), but against which we can design novel small molecule inhibitors to rescue the activity of the parent antibiotics. By integrating community-level analyses of microbiome perturbation and response, with mechanistic analyses of novel microbial resilience functions, we are improving the accuracy and sensitivity of genomics-based methods for diagnosing and treating pathogens and their resistance properties in the clinic and maintaining or rescuing healthy microbiome states.