The present work reports the effects of
caspofungin, a β-1,3-glucan synthase inhibitor, and
nikkomycin Z, an inhibitor of
chitin synthases, on two strains of Alternaria infectoria, a melanized fungus involved in opportunistic human
infections and respiratory
allergies. One of the strains tested, IMF006, bore phenotypic traits that conferred advantages in resisting antifungal treatment. First, the resting cell wall
chitin content was higher and in response to
caspofungin, the
chitin level remained constant. In the other strain, IMF001, the
chitin content increased upon
caspofungin treatment to values similar to basal IMF006 levels. Moreover, upon
caspofungin treatment, the FKS1 gene was upregulated in IMF006 and downregulated in IMF001. In addition, the resting β-
glucan content was also different in both strains, with higher levels in IMF001 than in IMF006. However, this did not provide any advantage with respect to
echinocandin resistance. We identified eight different
chitin synthase genes and studied relative gene expression when the fungus was exposed to the antifungals under study. In both strains, exposure to
caspofungin and
nikkomycin Z led to modulation of the expression of class V and VII
chitin synthase genes, suggesting its importance in the robustness of A. infectoria. The pattern of A. infectoria phagocytosis and activation of murine macrophages by spores was not affected by
caspofungin. Monotherapy with
nikkomycin Z and
caspofungin provided only fungistatic inhibition, while a combination of both led to fungal cell lysis, revealing a strong synergistic action between the
chitin synthase inhibitor and the β-
glucan synthase inhibitor against this fungus.