Khatmiamycin, a motility inhibitor and zoosporicide against the grapevine downy mildew pathogen Plasmopara viticola from Streptomyces sp. ANK313

Abstract

Peronosporomycetes are distinct from fungi and are phylogenetic relatives of brown algae and diatoms. They cause many destructive diseases in plants, animals, fishes and humans.1,2 One of the most notorious members of peronosporomycetes, Plasmopara viticola, is an obligate biotroph and a serious pathogen of grapevine worldwide. Many fungicides are ineffective against this phytopathogen, and hence, bioactive compounds with new modes of action are needed to combat this economically important pest. Under favorable environmental conditions, the fungus-like stramenopile, P. viticola infects grapevine leaves through characteristic biflagellate motile zoospores released from airborne sporangia coming from other infected plants. The zoospores aggregate to stomata of the grapevine leaf by swimming through water film and then rapidly encyst to become round cystospores by shedding their flagella.3,4 The cystospores then rapidly germinate to form germ tubes and penetrate host tissue through the stomata. Disruption of any of these asexual stages eliminates the potential for pathogenesis.5 The success of any zoosporic pathogen can be attributed in part to the speed of asexual differentiation to generate bi-flagellated motile zoospores and their ability to find a host through chemotaxis.6 Therefore, compounds that can interfere with normal swimming behavior and early development of P. viticola are supposed to be important as lead compounds in the management of this notorious phytopathogen.4 Streptomycetes are known to produce diverse groups of interesting bioactive secondary metabolites.7 In the course of screening for secondary metabolites from actinomycetes, we found that the crude extract of a terrestrial Streptomyces sp. ANK313 remarkably inhibited motility of P. viticola zoospores and caused subsequent lysis at 100 mgml_1. This observation prompted us to isolate and characterize the motility-inhibitory and lytic factors in the extracts by chromatographic fractionation. We have discovered a new motility inhibitor and zoosporicide named khatmiamycin (1) along with five known compounds from extracts of the culture broth of Streptomyces sp. ANK313. This study describes the isolation, structure elucidation and biological activity of khatmiamycin (1) and further known compounds towards zoospores of Plasmopara viticola.