Elucidating ecological mechanisms for propagation of antibiotic resistance genes via massively parallelized single-cell sequencing

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PROJECT SUMMARY The accelerating emergence of antibiotics resistant bacteria has become a global health crisis, costing tens of thousands of lives and hundreds of billions of dollars every year. Horizontal transfer of antibiotics resistance genes (ARGs) is a key mechanism driving the emergence of antibiotic resistant strains, but the ecological processes impacting the transmission of these genes through microbial communities are largely unknown. To address this knowledge gap, we propose to develop an ultrahigh-throughput single cell sequencing technology to identify the associations between ARGs and microbial taxa. This method will be used to decipher the time- dependent horizontal gene transfer networks underlying ARG spread in a human gut microbiome in response to clinically relevant antibiotics. The new technology will enable single cell analysis of microbial communities at an unprecedented scale. Deciphering the horizontal gene transfer networks responsible for ARG dissemination will deepen our understanding of the ecological interactions involved in the emergence of antibiotic resistant bacteria and inform the design of interventions to substantially reduce ARG propagation. A detailed understanding of the environmental and ecological factors influencing horizontal gene transfer is critical to combating infectious diseases.