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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


Alternative Oxidase: From Molecule and Function to Future Inhibitors

Author(s): Li J; Yang S; Wu Y; Wang R; Liu Y; Liu J; Ye Z; Tang R; Whiteway M; Lv Q; Yan L;

In the respiratory chain of the majority of aerobic organisms, the enzyme alternative oxidase (AOX) functions as the terminal oxidase and has important roles in maintaining metabolic and signaling homeostasis in mitochondria. AOX endows the respiratory system with flexibility in the coupling among the carbon metabolism pathway, electron transport chain (E ...

Article GUID: 38524433


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


Screening non-conventional yeasts for acid tolerance and engineering Pichia occidentalis for production of muconic acid

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

Saccharomyces cerevisiae is a workhorse of industrial biotechnology owing to the organism's prominence in alcohol fermentation and the suite of sophisticated genetic tools available to manipulate its metabolism. However, S. cerevisiae is not suited to overproduce many bulk bioproducts, as tox ...

Article GUID: 37652930


Candidiasis: from cutaneous to systemic, new perspectives of potential targets and therapeutic strategies

Author(s): Lu H; Hong T; Jiang Y; Whiteway M; Zhang S;

Candidiasis is an infection caused by fungi from a Candida species, most commonly Candida albicans. C. albicans is an opportunistic fungal pathogen typically residing on human skin and mucous membranes of the mouth, intestines or vagina. It can cause a wide variety of mucocutaneous barrier and systemic infections; and becomes a severe health problem in HI ...

Article GUID: 37307922


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


Rosemary essential oil and its components 1,8-cineole and α-pinene induce ROS-dependent lethality and ROS-independent virulence inhibition in Candida albicans

Author(s): Shahina Z; Al Homsi R; Price JDW; Whiteway M; Sultana T; Dahms TES;

The essential oil from Rosmarinus officinalis L., a composite mixture of plant-derived secondary metabolites, exhibits antifungal activity against virulent candidal species. Here we report the impact of rosemary oil and two of its components, the monoterpene a-pinene and the monoterpenoid 1,8-cineole, against Candida albicans, which induce ROS-dependent c ...

Article GUID: 36383525


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