Precise genome editing underlines the distinct contributions of mutations in , , , and genes to antifungal resistance in .

has recently emerged as a major threat due to the worldwide emergence of fluconazole-resistant strains causing clonal outbreaks in hospitals and poses a therapeutic challenge due to the limited antifungal armamentarium. Here, we used precise genome editing using CRISPR-Cas9 to gain further insights into the contribution of mutations in , , , and genes and the influence of allelic dosage to antifungal resistance in . Seven of the most common amino acid substitutions previously reported in fluconazole-resistant clinical isolates (including Y132F in ) were engineered in two fluconazole-susceptible lineages (ATCC 22019 and STZ5).

Antifungal efficacy of imidazo[1,2-]pyrazine-based thiosemicarbazones and thiazolidinediones against species.

To evaluate antifungal potential of 5,6,7,8-tetrahydroimidazo[1,2-]pyrazine hybrids based on thiosemicarbazones and thiazolidinediones against pathogenic species. Antifungal activity of nine compounds were assessed by broth microdilution. Interactions between active compounds and itraconazole were evaluated by the checkerboard assay using non-wild-type isolates.

Fungal Sterol Analyses by Gas Chromatography-Mass Spectrometry Using Different Derivatives.

Sterols are the main components of the fungal membrane. Their study can be used to describe the chemical biodiversity among the strains and species or to work on antifungal treatment. Those molecules can be analyzed by gas chromatography coupled with mass spectrometry (GC-MS) as free molecules or after derivation as acetate or trimethylsilyl ether (TMSi).

Impact of TR/L98H, TR/Y121F/T289A and TR Alterations in Azole-Resistant on Sterol Composition and Modifications after In Vitro Exposure to Itraconazole and Voriconazole.

Background: Sterols are the main components of fungal membranes. Inhibiting their biosynthesis is the mode of action of azole antifungal drugs that are widely used to treat fungal disease including aspergillosis. Azole resistance has emerged as a matter of concern but little is known about sterols biosynthesis in azole resistant .

Dibenzofuran Derivatives Inspired from Cercosporamide as Dual Inhibitors of Pim and CLK1 Kinases.

Pim kinases (proviral integration site for Moloney murine leukemia virus kinases) are overexpressed in various types of hematological malignancies and solid carcinomas, and promote cell proliferation and survival. Thus, Pim kinases are validated as targets for antitumor therapy. In this context, our combined efforts in natural product-inspired library generation and screening furnished very promising dibenzo[,]furan derivatives derived from cercosporamide.