Hypoxylon pulicidum sp. nov., a pantropical insecticide-producing endophyte

Nodulisporic acids (NAs) are indole diterpenes exhibiting potent systemic efficacy against blood-feeding arthropods, e.g. fleas and ticks, by binding arthropod-specific glutamate-gated chloride channels. Medicinal chemistry efforts employing a NAs template has led to the development of N-tert-butyl nodulisporamide as a candidate for a monthly treatment of fleas and ticks. NAs originate from a monophyletic lineage of tropical asexual fungal strains, identified as a Nodulisporium species (Xylariales), and hypothesized to be the asexual state of a Hypoxylon species. Inferences from GenBank sequences indicated that other researchers have encountered the same Nodulisporium endophytes. Cultures from a wood-inhabiting Hypoxylon from Martinique belonged to the same monophyletic clade. The conspecificity of the Hypoxylon collections and the NAs-producing endophytes was tested by mass spectrometry of metabolite profiles, multi-gene phylogenies, and phenotypic comparisons. A new species, H. pulicidum, is proposed. Life cycle reconstruction now permits location of fungus populations, their study in situ, and investigation of how NAs insecticides aid survival of the fungus.