Bacterial droplet-based single-cell RNA-seq reveals antibiotic-associated heterogeneous cellular states

In this study, we introduce BacDrop, a bacterial droplet-based high throughput scRNA-seq technology that can be applied to large cell numbers. We applied BacDrop to study Klebsiella pneumoniae clinical isolates and elucidated their critical, genome-wide heterogeneity in the absence and presence of antibiotic perturbations. An antibiotic-susceptible K. penumoniae isolate, MGH66, was treated separately with three different antibiotics, including meropenem, ciprofloxacin, and gentamicin. BacDrop was applied to these three samples as well as the untreated control. We profiled the within population heterogeneity in these 4 samples. In addition, we also applied BacDrop to a multi-drug resistant K. pneumoniae BIDMC35, and demonstrated the within population heterogeneity in this strain.