The echinocandin B producer fungus Aspergillus nidulans var. roseus ATCC 58397 does not possess innate resistance against its lipopeptide antimycotic.

Aspergillus nidulans var. roseus ATCC 58397 is an echinocandin B (ECB) producer ascomycete with great industrial importance. As demonstrated by ECB/caspofungin sensitivity assays, A. nidulans var. roseus does not possess any inherent resistance to echinocandins, and its tolerance to these lipopeptide antimycotics are even lower than those of the non-producer A. nidulans FGSC A4 strain. Under ECB producing conditions or ECB exposures, A. nidulans var. roseus induced its ECB tolerance via up-regulating elements of the chitin biosynthetic machinery and, hence, through changing dynamically the composition of its own cell wall. Importantly, although the specific ß-1,3-glucan synthase activity was elevated, these changes reduced the ß-glucan content of hyphae considerably, but the expression of fksA, encoding the catalytic subunit of ß-1,3-glucan synthase, the putative target of echinocandins in the aspergilli, was not affected. These data suggest that compensatory chitin biosynthesis is the centerpiece of the induced ECB tolerance of A. nidulans var. roseus. It is important to note that the induced tolerance to ECB (although resulted in paradoxical growth at higher ECB concentrations) was accompanied with reduced growth rate and, under certain conditions, even sensitized the fungus to other stress-generating agents like SDS. We hypothesize that although ECB-resistant mutants may arise in vivo in A. nidulans var. roseus cultures, their widespread propagation is severely restricted by the disadvantageous physiological effects of such mutations.