Figure 4 | Scientific Reports

Figure 4

From: Novel inhibitors of Mycobacterium tuberculosis GuaB2 identified by a target based high-throughput phenotypic screen

Figure 4

A change in strategy for Mtb drug discovery.

Recent innovations in screening technologies and robotics have heralded a change in strategy for primary antimicrobial drug discovery. Efforts to design inhibitors of specific bacterial targets as potential drugs (Target to Drug) have given way to the screening of substantial compound libraries for whole cell activity and subsequent target identification (Drug to Target). The former strategy lacks efficacy, as biochemical inhibitory activity does not necessarily translate to whole cell inhibitory activity. The latter, produces a vast array of antimicrobial compounds, however their mode of action is often not conducive to their progression as clinically relevant drugs. Here we have employed a combined strategy, screening for phenotypic resistance caused by over-expression of a mycobacteria-specific drug target, GuaB2, in M. bovis BCG. The outputs of this approach are compounds with confirmed whole cell activity and with a mode of action conducive to further development from compounds to drugs.

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