Discovery and characterization of low molecular weight inhibitors of Erwinia tracheiphila.

Plant pathogenic bacteria in the genus Erwinia cause economically important diseases, including bacterial wilt of cucurbits caused by E. tracheiphila (Et). Conventional bactericides are insufficient to control this disease. Using high-throughput screening 464 small molecules (SMs) with either cidal or static activity at 100 µM against a cucumber strain of Et were identified. Among them, 20 SMs (SM1-20), composed of nine distinct chemical moiety structures, were cidal to multiple Et strains at 100 µM. These lead SMs had low toxicity to human cells and honey bees at 100 µM. No phytotoxicity was observed on melon plants at 100 µM, except when SM12 was mixed with Silwet L-77 and foliar-sprayed, or when delivered through the roots. Lead SMs did not inhibit the growth of beneficial Pseudomonas and Enterobacter species but inhibited the growth of Bacillus species. Nineteen SMs were cidal to Xanthomonas cucurbitae and showed >50% growth inhibition against P. syringae pv. lachrymans. In addition, 19 SMs were cidal or static against E. amylovora in vitro. Five SMs demonstrated potential to suppress Et when foliar-sprayed on melon plants at 2X the minimum bactericidal concentration (MBC). Thirteen SMs reduced Et load in melon plants when delivered via roots. Temperature and light did not affect the activity of SMs. In vitro cidal activity was observed after 3 to 10 h exposure to these five SMs. Here we report 19 SMs that provide chemical scaffolds for future development of bactericides against plant pathogenic bacterial species.