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Otilonium Bromide Exhibits Potent Antifungal Effects by Blocking Ergosterol Plasma Membrane Localization and Triggering Cytotoxic Autophagy in Candida Albicans

Author(s): Zhen C; Wang L; Feng Y; Whiteway M; Hang S; Yu J; Lu H; Jiang Y;

Candidiasis, which presents a substantial risk to human well-being, is frequently treated with azoles. However, drug-drug interactions caused by azoles inhibiting the human CYP3A4 enzyme, together with increasing resistance of Candida species to azoles, represent serious issues with this class of drug, making it imperative to develop innovative antifungal ...

Article GUID: 38995235


Pitavastatin Calcium Confers Fungicidal Properties to Fluconazole by Inhibiting Ubiquinone Biosynthesis and Generating Reactive Oxygen Species

Author(s): Li W; Feng Y; Feng Z; Wang L; Whiteway M; Lu H; Jiang Y;

Fluconazole (FLC) is extensively employed for the prophylaxis and treatment of invasive fungal infections (IFIs). However, the fungistatic nature of FLC renders pathogenic fungi capable of developing tolerance towards it. Consequently, converting FLC into a fungicidal agent using adjuvants assumes significance to circumvent FLC resistance and the perpetua ...

Article GUID: 38929106


Antimicrobial photodynamic therapy against a dual-species cariogenic biofilm using a ruthenium-loaded resin-based dental material

Author(s): Leite ML; Comeau P; Aghakeshmiri S; Lange D; Rodrigues LKA; Branda N; Manso AP;

Background: Streptococcus mutans and Candida albicans are associated with caries recurrence. Therefore, this study evaluated the combination of a Ru(II)-loaded resin-based dental material (RDM) and antimicrobial photodynamic therapy (aPDT) against a dual-species biofilm of S. mutans and C. albicans. Methods: An aPDT protocol was established evaluating Ru ...

Article GUID: 38395246


A Systematic Evaluation of Curcumin Concentrations and Blue Light Parameters towards Antimicrobial Photodynamic Therapy against Cariogenic Microorganisms

Author(s): Comeau P; Manso A;

Dental caries is a highly preventable and costly disease. Unfortunately, the current management strategies are inadequate at reducing the incidence and new minimally invasive strategies are needed. In this study, a systematic evaluation of specific light parameters and aqueous curcumin concentrations for antimicrobial photodynamic therapy (aPDT) was condu ...

Article GUID: 38140048


Understanding Fluconazole Tolerance in Candida albicans: Implications for Effective Treatment of Candidiasis and Combating Invasive Fungal Infections

Author(s): Feng Y; Lu H; Whiteway M; Jiang Y;

Fluconazole (FLC) tolerant phenotypes in Candida species contribute to persistent candidemia and the emergence of FLC resistance. Therefore, making FLC fungicidal and eliminating FLC tolerance are important for treating invasive fungal diseases (IFDs) caused by Candida species. However, the mechanisms of FLC tolerance in Candida species remain to be fully ...

Article GUID: 37918789


Candida albicans exhibits heterogeneous and adaptive cytoprotective responses to anti-fungal compounds

Author(s): Dumeaux V; Massahi S; Bettauer V; Mottola A; Dukovny A; Khurdia SS; Costa ACBP; Omran RP; Simpson S; Xie JL; Whiteway M; Berman J; Hallett MT;

Candida albicans, an opportunistic human pathogen, poses a significant threat to human health and is associated with significant socio-economic burden. Current antifungal treatments fail, at least in part, because C. albicans can initiate a strong drug tolerance response that allows some cells to ...

Article GUID: 37888959


The Adr1 transcription factor directs regulation of the ergosterol pathway and azole resistance in Candida albicans

Author(s): Shrivastava M; Kouyoumdjian GS; Kirbizakis E; Ruiz D; Henry M; Vincent AT; Sellam A; Whiteway M;

Transcription factors (TFs) play key roles in cellular regulation and are critical in the control of drug resistance in the fungal pathogen Candida albicans. We found that activation of the transcription factor C4_02500C_A (Adr1) conferred significant resistance against fluconazole. In Saccharomy ...

Article GUID: 37791798


Genome sequencing of 15 acid-tolerant yeasts

Author(s): Bagley JA; Pyne ME; Exley K; Kevvai K; Wang Q; Whiteway M; Martin VJJ;

We report draft genome sequences for 15 non-conventional Saccharomycotina yeast strains obtained from public culture repositories. Included in our collection are eight strains of Pichia with broad tolerance to dicarboxylic acids. The genome sequences of these strains will enable comparative genomics of acid-tolerant phenotypes and strain engineering of no ...

Article GUID: 37747226


A Small Molecule Inhibitor of Erg251 Makes Fluconazole Fungicidal by Inhibiting the Synthesis of the 14α-Methylsterols

Author(s): Lu H; Li W; Whiteway M; Wang H; Zhu S; Ji Z; Feng Y; Yan L; Fang T; Li L; Ni T; Zhang X; Lv Q; Ding Z; Qiu L; Zhang D; Jiang Y;

Fluconazole (FLC) is widely used to prevent and treat invasive fungal infections. However, FLC is a fungistatic agent, allowing clinical FLC-susceptible isolates to tolerate FLC. Making FLC fungicidal in combination with adjuvants is a promising strategy to avoid FLC resistance and eliminate the ...

Article GUID: 36475771


A Deep Learning Approach to Capture the Essence of Candida albicans Morphologies

Author(s): Bettauer V; Costa ACBP; Omran RP; Massahi S; Kirbizakis E; Simpson S; Dumeaux V; Law C; Whiteway M; Hallett MT;

We present deep learning-based approaches for exploring the complex array of morphologies exhibited by the opportunistic human pathogen Candida albicans. Our system, entitled Candescence, automatically detects C. albicans cells from differential image contrast microscopy and labels each detected ...

Article GUID: 35972285


Transcriptional Profiling of the Candida albicans Response to the DNA Damage Agent Methyl Methanesulfonate

Author(s): Feng Y; Zhang Y; Li J; Omran RP; Whiteway M; Feng J;

The infection of a mammalian host by the pathogenic fungus Candida albicans involves fungal resistance to reactive oxygen species (ROS)-induced DNA damage stress generated by the defending macrophages or neutrophils. Thus, the DNA damage response in C. albicans may contribute to its pathogenicity. Uncovering the transcriptional changes triggered by the DN ...

Article GUID: 35886903


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