FKS1 mutation associated with decreased echinocandin susceptibility of Aspergillus fumigatus following anidulafungin exposure.

Invasive aspergillosis (IA) is a potentially lethal infection that affects mostly immunocompromised patients caused by Aspergillus fumigatus. Echinocandins are a second-line therapy against IA, used as a salvage therapy as well as for empirical or prophylactic therapy. Although they cause lysis of growing hyphal tips, they are considered fungistatic against molds. In vivo echinocandins resistance is uncommon; however, its wide clinical use could shortly lead to the emergence of A. fumigatus resistance. The aims of the present work was to assess the development of reduced echinocandins susceptibility phenotype by a A. fumigatus strain and to unveil the molecular mechanism underlying such phenotype. We induced in vitro cross-resistance to echinocandins following exposure of A. fumigatus to anidulafungin. Stability of the resistant phenotype was confirmed after removal of anidulafungin pressure. The FKS1 gene was partially sequenced and a E671Q mutation was found. A computational approach suggests that it can play an important role in echinocandin resistance. Given the emerging importance of this mechanism for clinical resistance in pathogenic fungi, it would be prudent to be alert to the potential evolution of this resistant mechanism in Aspergillus spp infecting patients under echinocandins therapeutics.

Malassezia interaction with a reconstructed human epidermis: Keratinocyte immune response.

The immediate immune response developed by the keratinocytes against Malassezia yeasts has been addressed yielding conflicting results. This study aims the assessment of cytokines and antimicrobial peptides gene expression elicited by M. sympodialis and M. furfur once in contact with a reconstructed human epidermis. A yeast suspension was prepared in RPMI 1640 medium (Sigma-Aldrich, St. Louis, MO) supplemented with Tween 60 and oleic acid to obtain approximately 1 × 106 cells in a volume of 100 µL. Clinical isolates of M. sympodialis (from pityriasis versicolor) and M. furfur (from seborrhoeic dermatitis) were inoculated, separately, onto a reconstructed human epidermis. A distinct expression pattern was found between the two tested species, with a tendency for overexpression of pro-inflammatory cytokines very soon after infection, whereas no significant expression or gene downregulation was often noticed following 24 and 48 h of incubation. A possible Malassezia species-dependent immune response pattern is highlighted.