Azole Antifungal Resistance in Candida albicans and Emerging Non-albicans Candida Species

Abstract

Within the limited antifungal armamentarium, the azole antifungals are the most frequent class used to treat Candida infections. Azole antifungals such as fluconazole are often preferred treatment for many Candida infections as they are inexpensive, exhibit limited toxicity, and are available for oral administration. There is, however, extensive documentation of intrinsic and developed resistance to azole antifungals among several Candida species. As the frequency of azole resistant Candida isolates in the clinical setting increases, it is essential to elucidate the mechanisms of such resistance in order to both preserve and improve upon the azole class of antifungals for the treatment of Candida infections. This review examines azole resistance in infections caused by C. albicans as well as the emerging non-albicans Candida species C. parapsilosis, C. tropicalis, C. krusei, and C. glabrata and in particular, describes the current understanding of molecular basis of azole resistance in these fungal species.

Fluconazole impacts the extracellular matrix of fluconazole-susceptible and -resistant Candida albicans and Candida glabrata biofilms

“…These results were confirmed by the SEM images of CgS (Figure 10(D,E)) and CgR (Figure 11(D,E)), which showed that fewer cells and cell agglomerates were more sparsely distributed on the substrate. It has been reported that C. glabrata has a decreased intrinsic susceptibility to FLZ and other classes of azole antifungals [42,50,51]. Nevertheless, the results of the present study showed that biofilm formation with 40 µg/mL of FLZ for CgS and 1,280 µg/mL of FLZ for CgR can reduce the cell viability of these microorganisms.…”

“…FLZ is often a chosen treatment for Candida infections because of its low cost and availability for oral administration [42]. This drug prevents the biosynthesis of ergosterol through the cytochrome P450 enzyme 14-α demethylase, which catalyzes the conversion of lanosterol to ergosterol [43].…”

“…The reduction of ergosterol changes the fluidity of the membrane and the activity of numerous membrane-bound enzymes, hindering fungal growth and replication [43]. However, FLZ-resistance is rising in Candida species [42,44,45,46], requiring a better understanding of the action of this drug in Candida biofilms. Due to the mechanism of action of FLZ, variations in the architecture of the ECM may happen during Candida biofilm formation in presence of this medication [34,47].…”

Secondary Onychomycosis Development after Cosmetic Procedure-Case Report

“…The both triazoles similarly as rhodamine 6G are well known substrates for Saccharomyces cerevisiae Pdr5p [18] and Cdr1p which is its homologue in the cells of C. albicans [19]. The observed simultaneously resistance to both tested triazoles and rhodamine 6G allows rather to conclude about resistance phenotype generated by ef lux pumps than by genes associated with the ergosterol synthesis as even ERG3 or ERG11 [17]. An additional proof of the existence of this particular phenotype in the case of our isolate are the results of studies with tacrolimus.…”

“…There are different molecular mechanisms of azole resistance that were reviewed in the literature [17]. The both triazoles similarly as rhodamine 6G are well known substrates for Saccharomyces cerevisiae Pdr5p [18] and Cdr1p which is its homologue in the cells of C. albicans [19].…”