Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2180674 | Fungal Genetics and Biology | 2015 | 13 Pages |
Abstract
A double homozygous atc1Î/atc1Î/ntc1Î/ntc1Î mutant (atc1Î/ntc1Î KO) was constructed in the pathogen opportunistic yeast Candida parapsilosis by disruption of the two chromosomal alleles coding for NTC1 gene (encoding a neutral trehalase) in a Cpatc1Î/atc1Î background (atc1Î KO strain, deficient in acid trehalase). The Cpatc1Î/ntc1Î KO mutant failed to counteract the inability of Cpatc1Î cells to metabolize exogenous trehalose and showed a similar growth pattern on several monosaccharides and disaccharides. However, upon prolonged incubation in either rich medium (YPD) or nutrient-starved medium the viability of Cpatc1Î cells exhibited a sensitive phenotype, which was augmented by further CpNTC1/NTC1 disruption. Furthermore, Cpatc1Î/ntc1Î KO cells had difficulty in resuming active growth in fresh YPD. This homozygous mutant also lacked any in vitro measurable trehalase activity, whether acid or neutral, suggesting that a single gene codes for each enzyme. By contrast, in Cpatc1Î/ntc1Î KO strain the resistance to oxidative and heat stress displayed by atc1Î mutant was suppressed. Cpatc1Î/ntc1Î KO cells showed a significant decrease in virulence as well as in the capacity to form biofilms. These results point to a major role for acid trehalase (Atc1p) in the pathobiology of C. parapsilosis, whereas the activity of neutral trehalase can only partially counteract Atc1p deficiency. They also support the use of ATC1 and NTC1 genes as interesting antifungal targets.
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Authors
Ruth Sánchez-Fresneda, José P. Guirao-Abad, MarÃa Martinez-Esparza, Sergi Maicas, Eulogio ValentÃn, Juan-Carlos Argüelles,