The mechanism of fluconazole resistance in Candida tropicalis is still unclear. Recently, we isolated a fluconazole-resistant strain of C. tropicalis from the blood specimen of a patient with candidemia in China. In vitro antifungal susceptibility of the isolate was determined by using CLSI M27-A3 and E-test methods. The sequence of ERG11 gene was then analyzed, and the three-dimensional model of Erg11p encoded by ERG11 gene was also investigated. The sequencing of ERG11 gene revealed the mutation of A395T in this fluconazole-resistant isolate of C. tropicalis, resulting in the Y132F substitution in Erg11p. Sequence alignment and three-dimensional model comparison of Erg11ps showed high similarity between fluconazole-susceptible isolates of C. tropicalis and Candida albicans. The comparison of the three-dimensional models of Erg11ps demonstrated that the position of the Y132F substitution in this isolate of C. tropicalis is identical to the isolate of C. albicans with fluconazole resistance resulting from Y132F substitution in Erg11p. Hence, we ascertain that the Y132F substitution of Erg11p caused by A395T mutation in ERG11 gene confers the fluconazole resistance in C. tropicalis.
Aspergillus fumigatus is naturally exposed to a highly variable environment and subjected to various kinds of stresses. High-osmolarity glycerol mitogen-activated protein kinase (HOG-MAPK) pathway plays a crucial role in regulating cellular homeostasis in response to environmental changes. Here, we explored the contribution of HOG-MAPK pathway to the adaptive responses to thermal stress and other related stresses in A. fumigatus. We observed the phenotype features of wild-type strains and their derived mutants at 37 and 48 °C, and the results suggested that tcsB participates in response to high temperature. Furthermore, susceptibility test for antifungal drugs showed that SHO1 branch is probably involved in the susceptibility of A. fumigatus to itraconazole at high temperature. Although sakA expression at mRNA level appeared unchanged in wild-type AF293 subjected to thermal stress, phosphorylated SakAp level increased significantly in the strains exposed to cold stress, 250 mmol/L nystatin or 10 % dimethyl sulfoxide in a manner dependent on the SLN1 branch and independent on the SHO1 branch. Taken together, these results indicate that HOG-MAPK pathway, especially the SLN1 branch, plays an important role in the adaptations of A. fumigatus to thermal stress and other related stresses.
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