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.