Single-cell characterization of antibiotic-induced heteroresistance

Project Narrative Efforts at understanding how transcriptional heterogeneity contributes to antibiotic heteroresistance among isogenic bacteria have been hampered by lack of suitable tools and approaches. We propose to develop bacterial single-cell RNA sequencing technology to address this critical challenge in understanding transcriptional heterogeneity. Complemented by genome-wide functional genomic screens including systematic overexpression and CRISPR-interference, we anticipate these systems-wide strategies to discover novel transcriptional determinants of antibiotic resistance as potential drug targets.