TABLE 1.

Advantages and disadvantages of HTS

Screen type	Definition	Advantages	Disadvantages
Biochemical screens	In vitro assay to look for enzyme inhibition	More sensitivity; assay format can be simple	Only well-behaved targets (excluding membrane proteins); biological activity is not guaranteed; more nuisance compounds with nonspecific activity (PAINS)
WCSs (classic screens)	Bacterial assay to look for inhibitors of growth	Biological activity is guaranteed in the model organism; assay format can be simple	Target identification can take time; difficult to prioritize due to high hit rates (20–30%)
TB-WCSs	Bacterial assay to look for inhibition of desirable target(s) in a pathway	Biological activity is guaranteed in the model organism; assay format can be simple; on-target activity is expected; low hit rate, making it easier to focus on a few hits	Bacterial physiology must be well understood; requires a model organism with sufficient genetic tools