Fig. 1: PROSPECT screen on reference collection of compounds with known antibacterial activity and annotated MOA. | Nature Communications

Fig. 1: PROSPECT screen on reference collection of compounds with known antibacterial activity and annotated MOA.

From: Reference-based chemical-genetic interaction profiling to elucidate small molecule mechanism of action in Mycobacterium tuberculosis

Fig. 1

a Breakdown of the reference set, which comprises 437 compounds from 71 annotated mechanisms of action (MOAs) that target 9 high-level processes. b Schematic of the PROSPECT (PRimary screening Of Strains to Prioritize Expanded Chemistry and Targets) pipeline (Created in BioRender. Lab, H. (2025) https://BioRender.com/oa7xnfj). Barcoded hypomorph strains, depleted for one of Mtb’s essential proteins, are pooled, incubated for 14 days in 384-well plates containing the compound library, and then heat-killed and lysed. Barcodes are PCR amplified and amplicons sequenced to yield barcode counts as a measure of strain census in each well. Compound-induced Growth Rate (GR) for each strain in response to each condition is based on the ratio of condition- and vehicle- numbers of doublings. Strain distributions are then quantile normalized and robust z-scored across all conditions to calculate standardized growth rate (sGR). c Example standardized growth rate (sGR) chemical-genetic interaction (CGI) profiles across different concentrations of the fluoroquinolone nadifloxacin for 7 wild-type (WT) H37Rv barcoded strains (black), GyrA hypomorph (green), and 332 other hypomorphs in the pool (gray). Source data are provided as a Source Data file.

Back to article page