Two Sequential Clinical Isolates of with Multidrug-Resistance to Posaconazole and Echinocandins.

is one of the most prevalent causative pathogens of invasive candidiasis, and multidrug-resistant strains are emerging. We identified two clinical isolates of , BMU10720 and BMU10722 sequentially isolated from one patient with multidrug-resistance to posaconazole (POS), caspofungin (CAS), micafungin (MCF), and anidulafungin (ANF). Overexpression of in BMU10720 and in BMU10722 were detected at basal level. When exposed to POS, was significantly up-regulated in both isolates compared with susceptible reference strain, while was up-regulated considerably only in BMU10720. sequencing revealed that both isolates harbored P76S, P143T, and D243N substitutions, while was intact. Cdr1 inhibitor FK520 reversed POS-resistance by down-regulating expression. sequencing revealed that both isolates harbored S663P substitution in , and four single nucleotide polymorphisms (SNPs) existed in genes between BMU10720 and BMU10722, while was intact. Both and were up-regulated by CAS in BMU10720 and BMU10722. FK520 down-regulated expression induced by CAS through inhibiting calcineurin, resulting in synergic effect with echinocandins as well as Congo Red and Calcofluor White, two cell wall-perturbing agents. In conclusion, the multidrug-resistance of isolates in our study was conferred by different mechanisms. and overexpression in one isolate and only overexpression in the other isolate may mediate POS-resistance. S663P mutation in and up-regulation of may contribute to echinocandin-resistance in both isolates.