Echinocandins, the
lipopeptide class of
glucan synthase inhibitors, are an alternative to
ergosterol-synthesis inhibitors to treat
candidiasis and
aspergillosis. Their oral absorption, however, is low and they can only be used parenterally. During a
natural product screening program for novel types of
glucan synthesis inhibitors with improved bioavailability, a fungal extract was found that inhibited the growth of both a wild-type Saccharomyces cerevisiae strain and the null mutant of the FKS1 gene (fks1::HIS). The mutant strain was more sensitive to growth inhibition, suggesting that the fungal extract could contain an inhibitor of
glucan synthesis. A novel acidic
steroid, named
arundifungin, was purified from a fungal extract obtained from a liquid culture of Arthrinium arundinis collected in Costa Rica.
Arundifungin caused the same pattern of hallmark morphological alterations in Aspergillus fumigatus hyphae as
echinocandins, further supporting the idea that
arundifungin belongs to a new class of
glucan synthesis inhibitors. Moreover, its antifungal spectrum was comparable to those of
echinocandins and
papulacandins, preferentially inhibiting the growth of Candida and Aspergillus strains, with very poor activity against Cryptococcus.
Arundifungin was also detected in nine other fungal isolates which were ecologically and taxonomically unrelated, as assessed by sequencing of the ITS1 region. Further, it was also found in two more Arthrinium spp from tropical and temperate regions, in five psychrotolerant conspecific isolates collected on Macquarie Island (South Pacific) and belonging to the Leotiales, and in two endophytes collected in central Spain (a sterile fungus belonging to the Leotiales and an undetermined coelomycete).