ALS3 Expression as an Indicator for Candida albicans Biofilm Formation and Drug Resistance

Abstract

Resistance caused by the formation of the Candida albicans (C. albicans) biofilm is one of the main reasons for antifungal therapy failure. Thus, it is important to find indicators that predict C. albicans biofilm formation to provide evidence for the early prevention and treatment of the C. albicans biofilms. In this study, C. albicans samples were selected from C. albicans septicemia that were sensitive to common antifungal agents. It was found that the agglutinin-like sequence 3 (ALS3) gene was differentially expressed in free, antifungal, drug-sensitive C. albicans. The average ALS3 gene expression was higher in the C. albicans strains with biofilm formation than that in the C. albicans strains without biofilm formation. Then, it was further confirmed that the rate of biofilm formation was higher in the high ALS3 gene expression group than that in the low ALS3 gene expression group. It was found that C. albicans with biofilm formation was more resistant to fluconazole, voriconazole, and itraconazole. However, it maintained its sensitivity to caspofungin and micafungin in vitro and in mice. Further experiments regarding the prevention of C. albicans biofilm formation were performed in mice, in which only caspofungin and micafungin prevented C. albicans biofilm formation. These results suggest that the expression level of ALS3 in C. albicans may be used as an indicator to determine whether C. albicans will form biofilms. The results also show that the biofilm formation of C. albicans remained sensitive to caspofungin and micafungin, which may help to guide the selection of clinical antifungal agents for prevention and therapy.

Efficacy of Crude Extract from Streptomyces cellulosae Against Biofilm-Related Genes of Candida albicans

“…2024; 17(4): e145959. and preventive strategies (28), a finding that corroborates our results. Additionally, Martorano-Fernandes et al demonstrated that gene expression levels, including those of the ALS1, ALS3, and HWPa genes, could vary based on the environmental conditions and substances present, noting that increased gene expression could exacerbate pathogenic conditions (29).…”

A Comparative Study between Invasive and Superficial Candida albicans Infections Regarding Biofilm Formation, ALS3 and SAP1-6 Genes Expression and Anti-Fungal Drug Susceptibility

“…Our research revealed a relationship between the expression of ALS3 and the ability to biofilm formation with high statistically significant difference between ALS3 expression in biofilm forming and non-biofilm forming isolates. Similar results were documented by Deng et al 29 and Mohammed et al 33 The primary virulence determinants in C. albicans are secreted aspartic proteases, which are encoded by a family of 10 SAP genes 35 . Our result detected the SAP1-6 expression in all isolates.…”

“…Our study demonstrated a relation between the biofilm development and fluconazole and itraconazole resistance in C. albicans isolates, with statistically significant variations between those who develop biofilm and those who don't with more resistance to fluconazole and itraconazole. Similarly, Deng et al 29 reported that the resistance to fluconazole, vioriconazole and itraconazole was higher for C. albicans with biofilm formation. However, Marak & Dhanashree 30 found no statistical correlation between the biofilm development and antifungal sensitivity (p > 0.05).…”

Development and applications of a CRISPR activation system for facile genetic overexpression in Candida albicans

“…Given that our CRISPRa system has the benefit of exploiting a gene's endogenous promoter for overexpression, we next wanted to determine if our CRISPRa system could be used to promote enhanced expression of genes under conditions that already favored high gene expression. We focused on ALS3 , where expression levels are known to be significantly enhanced upon growth in conditions that favor filamentous or biofilm growth, such as growth in RPMI media at 37°C ( Bahn et al 2007 ; Ruben et al 2020 ; Deng et al 2021 ). We compared basal ALS3 transcript levels of the C. albicans control strain grown in YPD at 30°C compared with RPMI at 37°C via RT-qPCR, and confirmed that ALS3 exhibits ∼100-fold higher expression in RPMI at 37°C ( Fig.…”