Membrane fluidity and lipid composition of fluconazole resistant and susceptible strains of Candida albicans isolated from diabetic patients

Abstract

Ten clinical isolates of Candida albicans, five strains belonging to each of fluconazole resistant and susceptible groups isolated from diabetic patients, were studied for the membrane fluidity and lipid composition. Compared to fluconazole susceptible strains, fluconazole resistant ones exhibited enhanced membrane fluidity as measured by fluorescence polarization technique. The increased membrane fluidity was reflected in the decreased p-values exhibited by the resistant strains. On the other hand, susceptible isolates contained higher amount of ergosterol, almost twice as compared to resistant isolates which might have contributed to their lower membrane fluidity. However, no significant alteration was observed in the phospholipid and fatty acid composition of these isolates. Labeling experiments with fluorescamine dye revealed that the percentage of the exposed aminophospholipid, phosphatidylethanolamine was highest in the resistant strains as compared to the susceptible strains, indicating a possible overexpression of CDR1 and CDR2 genes in resistant strains. The results presented here suggest that the changes in the ergosterol content and overexpression of ABC transporter genes CDR1 and CDR2 could contribute to fluconazole resistance in C. albicans isolated from diabetic patients.

Synthetic Pesticides Used in Agricultural Production Promote Genetic Instability and Metabolic Variability in Candida spp.

“…It was shown that Cdr1p and Cdr2p represent two major drug extrusion pumps in C. albicans , effluxing not only azoles and their derivatives but also a wide variety of structurally unrelated compounds. Contrary to our studies, no significant alteration was observed in the phospholipid and fatty acid composition of the investigated C. albicans strains [ 71 , 72 ]. It can be assumed that pesticides can also be removed by the mentioned major drug extrusion pumps, but this requires further research.…”

Deletion of thePDR16gene influences the plasma membrane properties of the yeastKluyveromyces lactis

“…Indeed, changes in the structural properties of the K. lactis membrane (decreased sterol/phospholipid ratio, the decreased saturated fatty acid/monounsaturated fatty acid ratio) could explain the higher membrane fluidity, which represents higher resistance of the K. lactis yeast to several drugs compared with its Klpdr16⌬ mutant. Our results thus support the observations of Mishra et al (2008), who found increased membrane fluidity in fluconazole-resistant C. albicans clinical isolates from diabetic patients, and those of Younsi et al (2000), explaining higher membrane fluidity with changes in its lipid composition, representing a process of metabolic resistance of the K. lactis yeast to amphotericin B. The precise molecular function of KlPdr16p in providing protection against azole antifungals is not known yet and requires further experimentation.…”

Recreation of in-host acquired single nucleotide polymorphisms by CRISPR-Cas9 reveals an uncharacterised gene playing a role in Aspergillus fumigatus azole resistance via a non-cyp51A mediated resistance mechanism

“…In Candida albicans reductions in ergosterol levels have previously been associated with increased azole resistance (Kanafani and Perfect, 2008, Kelly et al, 1997, Kohli et al, 2002, Löffler et al, 2000, Mishra et al, 2008) . In addition, a collection of fluconazole resistant clinical C. albicans isolates were shown to possess defective sterol Δ 5,6 -desaturation, which resulted in alteration of membrane composition to include more 14α-methylfecosterol (Kanafani and Perfect, 2008, Kelly et al, 1997).…”