Development of Antivirulence Compounds: A Biochemical Review

There is an urgent requirement for new anti‐infective compounds that can be used to prevent or treat bacterial pathogens. In particular, Gram‐negative pathogens, which are most commonly associated with hospital‐acquired infections, are of major concern. In this review, we cover recent developments in the screening and testing of new anti‐infective compounds that interfere with aspects of bacterial pathogenicity. This so‐called antivirulence approach is very different to traditional antibiotic development and testing. Moreover, antivirulence compounds vary considerably in their chemical structures, ranging from small compounds to large natural products. The challenge of understanding the precise mechanism of action of any such compound is also highlighted. A wide range of anti‐infective compounds targeting virulence factor expression or function have been developed. The compounds range from small molecules to complex natural products: there is enormous diversity. The vast majority of these have resulted from high throughput screens and lack detailed mechanistic knowledge of their mode of action.