Biofilm Formation and Aspartyl Proteinase Activity and Their Association with Azole Resistance Among Candida albicans Causing Vulvovaginal Candidiasis, Egypt

Abstract

Background Candida albicans ( C. albicans ) is a major cause of vulvovaginal candidiasis (VVC), a condition that is commonly treated with azole agents. Biofilm formation and aspartyl proteinase production are important virulence factors that could be linked to azole resistance in C. albicans impeding therapy. Aim To find out the association of both factors with azole resistance among C. albicans isolated from VVC cases in Egyptian nonpregnant women of childbearing age. Patients and Methods In a cross-sectional study, C. albicans was isolated from nonpregnant females diagnosed clinically as having VVC during a 1-year study period. Susceptibility to azole agents was tested using the disc diffusion method. Biofilm formation and aspartyl proteinase production were assessed phenotypically. Additionally, two biofilm-related genes ( ALS1 and HWP1 ) and three proteinase genes ( SAP2, SAP4 , and SAP6 ) were screened for using polymerase chain reaction (PCR). Results Among 204 C. albicans isolates, azole resistance ratios were as follows: voriconazole (30.4%), itraconazole (17.6%), fluconazole (11.3%) and econazole (6.4%). Biofilm-producing capacity was detected in 63.2% of isolates, and 63.2% were proteinase producers. The frequencies of ALS1 and HWP1 were 69.6% and 74.5%, respectively, while SAP2, SAP4 , and SAP6 were 69.2%, 88.7%, and 64.7%, respectively. Biofilm formation was significantly associated with azole resistance (P < 0.001 for each tested azole agent) as was proteinase production (P < 0.001 for fluconazole, voriconazole, and econazole resistance and P = 0.047 for itraconazole). Conclusion Among nonpregnant Egyptian women of childbearing age, azole resistance in C. albicans causing VVC is significantly associated with biofilm formation and proteinase production. The development of new therapeutic agents that can target these factors is warranted.

Secreted Aspartic Proteinases: Key Factors in Candida Infections and Host-Pathogen Interactions

“…All tested C. albicans isolates resistant to the three above-mentioned drugs and collected from patients with systemic infections produced Sap9, Sap10, or both proteinases [147]. Biofilm formation and the production of Sap2, Sap4, and Sap6 have been shown to be associated with resistance to azoles in patients with vulvovaginal candidiasis [148].…”

Biofilm Formation and Antifungal Susceptibility Profile of Candida Species Responsible for Vulvovaginal Candidiasis in Pregnant and Non-Pregnant Women visiting a Tertiary Care Hospital in Southern India

“…It is thus critical for researchers to contribute to the existing knowledge on Candida biofilm prevalence and antifungal resistance, as both of these Candidal attributes have been evolving considerably over the years. [16][17][18][19] Furthermore, these are bound to alter based on the study population and its dynamics. 13,18 Although several studies have demonstrated an increase in fluconazole resistance in VVC cases worldwide, there are only a limited number of studies that emphasize the evolving resistance of Candida species to other antifungals such as itraconazole, amphotericin B, and voriconazole.…”