Genomic Variation-Mediating Fluconazole Resistance in Yeast

Wang, Wenyao; Cai, Hong‐Qing; Qu, Si-Yuan; Lin, Wei‐Hao; Liang, Chengcheng; Líu, Hao; Xie, Ze‐Xiong; Yang, Yuan

doi:10.3390/biom12060845

Cited by 10 publications

(5 citation statements)

References 52 publications

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“…However, Esc7 did not show large changes to CDR1 , CDR2 , or MDR1 expression in the conditions we examined. Previously this was thought to be part of the mechanism of fluconazole resistance in strains with Chr3 trisomies as CDR1 , CDR2 , and MRR1 reside on Chr3 [ 59 , 85 ].…”

Section: Discussionmentioning

confidence: 99%

Selection of ethanol tolerant strains of Candida albicans by repeated ethanol exposure results in strains with reduced susceptibility to fluconazole

Day,

Kumamoto

2024

PLoS ONE

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Candida albicans is a commensal yeast that has important impacts on host metabolism and immune function, and can establish life-threatening infections in immunocompromised individuals. Previously, C. albicans colonization has been shown to contribute to the progression and severity of alcoholic liver disease. However, relatively little is known about how C. albicans responds to changing environmental conditions in the GI tract of individuals with alcohol use disorder, namely repeated exposure to ethanol. In this study, we repeatedly exposed C. albicans to high concentrations (10% vol/vol) of ethanol—a concentration that can be observed in the upper GI tract of humans following consumption of alcohol. Following this repeated exposure protocol, ethanol small colony (Esc) variants of C. albicans isolated from these populations exhibited increased ethanol tolerance, altered transcriptional responses to ethanol, and cross-resistance/tolerance to the frontline antifungal fluconazole. These Esc strains exhibited chromosomal copy number variations and carried polymorphisms in genes previously associated with the acquisition of fluconazole resistance during human infection. This study identifies a selective pressure that can result in evolution of fluconazole tolerance and resistance without previous exposure to the drug.

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Section: Discussionmentioning

confidence: 99%

Selection of ethanol tolerant strains of Candida albicans by repeated ethanol exposure results in strains with reduced susceptibility to fluconazole

Day,

Kumamoto

2024

PLoS ONE

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“…The most common resistance mechanisms are molecular mutations of the antifungal enzyme target, alteration of enzymes related to ergosterol synthesis, and alterations in efflux pumps, ATP binding cassette (ABC), or major facilitators (MF) [92][93][94][95] For instance, azole resistance of Candida and Aspergillus species generally occurs by two main mechanisms: Alteration of genes in the metabolic pathways of ergosterol synthesis and changes in drug efflux [95]. Overexpression of the ERG11 gene has been observed in several Candida species, such as C. albicans, C. parapsilosis, and C. tropicalis [96].…”

Section: Susceptibility Resistance To Antifungals and Resistant Fungi...mentioning

confidence: 99%

Alternative and Classical Processes for Disinfection of Water Polluted by Fungi: A Systematic Review

Caicedo-Bejarano,

Morante-Caicedo,

Castro-Narváez

et al. 2024

Water

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The introduction of the first list of priority pathogenic fungi by the World Health Organization stresses the need to research and develop public health actions to mitigate infections caused by fungi. One of those actions involves the water disinfection systems, which comprise classical and alternative methods that have been developed in the last decades. Thereby, this work reviews the disinfection of fungi by classical methods such as chlorination, ozonation, and ultraviolet (UV) treatments and alternative advanced oxidation processes (AOPs) such as photo-Fenton, photocatalysis, or couplings of UV with peroxides. The matrices of aquatic systems (sewage, groundwater, drinking water, among others) were considered. A bibliometric analysis is performed initially, and then some aspects of the resistance to antifungals are presented, and the efficiency of the diverse processes in the reduction in fungal loading is also revised. Herein, it is shown the role of the disinfecting agents (e.g., chlorine, hydroxyl radical, or light) and their effects on fungi structures (e.g., direct DNA damage, or indirect damage due to the action of radicals). Moreover, gaps, such as the treatment of antifungal-resistant fungi and limited information about combinations among AOPs, related to the disinfection of water polluted by fungi, were identified.

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“…The genus examined may also affect the results seen with azoles. Fluconazole and itraconazole both block the 14-demethylase in Cryptococcus neoformans, which leads to a buildup of methylated sterol precursors (Wang et al, 2022;Debnath et al, 2017). To a far greater extent than in fungi, azoles suppress mammalian cholesterol production at the 14-demethylation stage (Aderiye and Oluwole, 2015).…”

Section: Mechanism Of Action Of Allylaminesmentioning

confidence: 99%

Antifungal chemicals promising function in disease prevention, method of action and mechanism

Dominguez,

Luque-Vilca,

Mallma

et al. 2023

Braz. J. Biol.

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The increasing use of antimicrobial drugs has been linked to the rise of drug-resistant fungus in recent years. Antimicrobial resistance is being studied from a variety of perspectives due to the important clinical implication of resistance. The processes underlying this resistance, enhanced methods for identifying resistance when it emerges, alternate treatment options for infections caused by resistant organisms, and so on are reviewed, along with strategies to prevent and regulate the formation and spread of resistance. This overview will focus on the action mechanism of antifungals and the resistance mechanisms against them. The link between antibacterial and antifungal resistance is also briefly discussed. Based on their mechanism action, antifungals are divided into three distinct categories: azoles, which target the ergosterol synthesis; 5-fluorocytosine, which targets macromolecular synthesis and polyenes, which interact physiochemically with fungal membrane sterols. Antifungal resistance can arise through a wide variety of ways. Overexpression of the target of the antifungal drug, changes to the drug target, changes to sterol biosynthesis, decreased intercellular concentration of the target enzyme, and other processes. A correlation exists between the mechanisms of resistance to antibacterial and antifungals, despite the fact that the comparison between the two is inevitably constrained by various parameters mentioned in the review. Drug extrusion via membrane pumps has been thoroughly documented in both prokaryotic and eukaryotic cells, and development of new antifungal compounds and strategies has also been well characterized.

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Genomic Variation-Mediating Fluconazole Resistance in Yeast

Cited by 10 publications

References 52 publications

Selection of ethanol tolerant strains of Candida albicans by repeated ethanol exposure results in strains with reduced susceptibility to fluconazole

Selection of ethanol tolerant strains of Candida albicans by repeated ethanol exposure results in strains with reduced susceptibility to fluconazole

Alternative and Classical Processes for Disinfection of Water Polluted by Fungi: A Systematic Review

Antifungal chemicals promising function in disease prevention, method of action and mechanism

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