1887

Abstract

. Fungal infections have increased in recent decades, with being the fourth most common aetiological agent of nosocomial infections. Disaccharide trehalose has been proposed as a target for the development of new antifungals. In we have examined the susceptibility shown by two mutants deficient in trehalose biosynthesis, namely and , to amphotericin B (AmB) and micafungin (MF).

. Minimum inhibitory concentrations (MICs) were calculated according to the Clinical and Laboratory Standards Institute (CLSI) criteria. Cell viability was assessed by cell counting. Intracellular reactive oxygen species (ROS) and the mitochondrial membrane potential were measured by flow cytometry, while the trehalose content and biofilm formation were determined by enzymatic assays.

. While the mutant was highly sensitive to AmB exposure, its resistance to MF was similar to that of the wild-type. Notably, the opposite phenotype was recorded in the mutant. In turn, MF induced a significant level of endogenous ROS production in the parental SC5314 and cells, whereas the ROS formation in cells was virtually undetectable. The level of endogenous ROS correlated positively with the rise in mitochondrial activity. Only AmB was able to promote intracellular synthesis of trehalose in the parental strain; it was absent from cells and showed low levels in , confirming the unspecific dephosphorylation of trehalose-6P in . Furthermore, the capacity of both and mutants to form biofilms was drastically reduced after AmB exposure, whereas it increased in cells treated with MF.

. Our data lend weight to the idea of using trehalose biosynthesis as a potential target for antifungal therapy.

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2019-10-01
2019-10-24
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