Antimicrobial activity of ergokonin A from Trichoderma longibrachiatum

Aims: Natural fungal products were screened for antifungal compounds. The m ode of action of one of the hits found and the taxonomy of the producing or ganism were analysed. Methods and Results: An extract from a Trichoderma species showed a more po tent activity in an agar-based assay against the null mutant fks1::HIS stra in than against the wild-type strain, suggesting that it could contain a gl ucan synthesis inhibitor. The active component was identified as the known compound ergokonin A. The compound exhibited activity against Candida. and Aspergillus species, but was inactive against Cryptococcus species. It indu ced alterations in the hyphal morphology of Aspergillus fumigatus. The iden tification of the producing isolate was confirmed by sequencing of the rDNA internal transcribed spacers and comparison with the sequences of other Tr ichoderma. species. The analysis showed that the producing fungus had a hig h homology with other strains classified as Trichoderma longibrachiatum and its teleomorph Hypocrea schweinitzii. Conclusions: The antifungal activity spectrum of ergokonin A and the morpho logy alterations induced on A. fumigatus are consistent with glucan synthes is as the target for ergokonin A. The production of ergokonin A is not unco mmon, but is probably restricted to Trichoderma species. Significance and Impact of the Study: The discovery that ergokonin A could be an inhibitor of glucan synthesis, having a structure very different to o ther inhibitors, increases the likelihood that orally active agents with th is fungal-specific mode of action may be developed.