Abstract
Pdr16p is considered a factor of clinical azole resistance in fungal pathogens. The most distinct phenotype of yeast cells lacking Pdr16p is their increased susceptibility to azole and morpholine antifungals. Pdr16p (also known as Sfh3p) of Saccharomyces cerevisiae belongs to the Sec14 family of phosphatidylinositol transfer proteins. It facilitates transfer of phosphatidylinositol (PI) between membrane compartments in in vitro systems. We generated Pdr16pE235A, K267A mutant defective in PI binding. This PI binding deficient mutant is not able to fulfill the role of Pdr16p in protection against azole and morpholine antifungals, providing evidence that PI binding is critical for Pdr16 function in modulation of sterol metabolism in response to these two types of antifungal drugs. A novel feature of Pdr16p, and especially of Pdr16pE235A, K267A mutant, to bind sterol molecules, is observed.
Highlights
Azole antifungals are often the primary choice in treating fungal infections
To address the question to which extent the PI binding ability of Pdr16p is relevant to its function in relation to azole resistance, we generated Pdr16pE235A, K267A mutant defective in PI binding. We show that this PI binding-deficient mutant is not able to fulfill the role of Pdr16p in providing protection against azole antifungals, establishing PI binding as an essential feature of Pdr16p
Our results show that pdr16Δ strain and pdr16Δ strain containing pdr16 E235A, K267A allele defective in PI binding are more susceptible to amorolfine but not terbinafine compared to their parental wild-type strain FY 1679-28c
Summary
Azole antifungals are often the primary choice in treating fungal infections. Yeast and fungi are able to develop resistance to counteract the action of azoles. Deletion of CaPDR16 in azole-resistant clinical isolates decreased their resistance to azoles approximately two-fold [4,5]. Overexpression of CaPDR16 resulted in yeast cells approximately two-fold more resistant to fluconazole compared to parental, azole-susceptible cells. These results implicate Pdr16p in low-level resistance of C. albicans to azoles [4]. In another clinically important opportunistic yeast pathogen, Candida glabrata, pdr16Δ mutation increased the susceptibility of yeast cells to azole antifungals and reduced cell surface hydrophobicity and biofilm production [6]. Pdr16p could be considered as one of the targets in preventing adverse azole resistance in fungi
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callMore From: Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
