Quercetin Assists Fluconazole to Inhibit Biofilm Formations of Fluconazole-Resistant Candida Albicans in In Vitro and In Vivo Antifungal Managements of Vulvovaginal Candidiasis

Abstract

Background: Vulvovaginal candidiasis (VVC) is a common gynecological disease. Candida albicans is believed to be mainly implicated in VVC occurrence, the biofilm of which is one of the virulence factors responsible for resistance to traditional antifungal agents especially to fluconazole (FCZ). Quercetin (QCT) is a dietary flavonoid and has been demonstrated to be antifungal against C. albicans biofilm. Methods: 17 C. albicans isolates including 15 clinical ones isolated from VVC patients were employed to investigate the effects of QCT and/or FCZ on the inhibition of C. albicans biofilm. Results: We observed that 64 µg/mL QCT and/or 128 µg/mL FCZ could (i) be synergistic against 10 FCZ-resistant planktonic and 17 biofilm cells of C. albicans, (ii) inhibit fungal adherence, cell surface hydrophobicity (CSH), flocculation, yeast-to-hypha transition, metabolism, thickness and dispersion of biofilms; (iii) down-regulate the expressions of ALS1, ALS3, HWP1, SUN41, UME6 and ECE1 and up-regulate the expressions of PDE2, NRG1 and HSP90, and we also found that (iv) the fungal burden was reduced in vaginal mucosa and the symptoms were alleviated in a murine VVC model after the treatments of 5 mg/kg QCT and/or 20 mg/kg FCZ. Conclusion: Together with these results, it could be demonstrated that QCT could be a favorable antifungal agent and a promising synergist with FCZ in the clinical management of VVC caused by C. albicans biofilm.

Vulvovaginal candidiasis: histologic lesions are primarily polymicrobial and invasive and do not contain biofilms

“…In fact, some clinicians refer to Candida vaginitis as infection of vaginal secretions only. Moreover, the histological appearance of nonvaginal Candida lesions presented in some publications are all definitively invasive (Gow and Hube, 17 page 407, Figure 1, A, B, and C, and Figure 2; Jabra-Rizk et al, 18 page 2729, Figure 9, B and C; Gao et al, 6 page 737, Figure 9; Allison et al, 7 page 8, Figure 6) and similar to our findings.…”

Antifungal Activity of Gallic Acid In Vitro and In Vivo

“…Fluconazole is widely used clinically for treating pathogenic fungal infection, and specifically by C. albicans (Gao et al, ). It is a specific and selective inhibitor of fungal SE and inhibits sterol 14α‐demethylase cytochrome P450 at later steps in the ergosterol pathway (Warrilow et al, ).…”

The Interaction of N-Acetylcysteine and Serum Transferrin Promotes Bacterial Biofilm Formation

“…They can also be found on soft tissues, with notable examples including the Pseudomonas aeruginosa biofilms in cystic fibrosis (CF) patients and the bacterial biofilms that develop on chronic wound surfaces such as diabetic foot ulcers and burns [2-5]. Because biofilms can effectively shield pathogens from host immune responses and antimicrobial treatment, and may lead to refractory infections or biofilm-associated diseases, they present a great health risk [6, 7]. …”