State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences Beijing, China.
Published: June 2013
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Article Abstract
Antifungal azoles inhibit ergosterol biosynthesis by interfering with lanosterol 14α-demethylase. In this study, seven upregulated and four downregulated ergosterol biosynthesis genes in response to ketoconazole treatment were identified in Neurospora crassa. Azole sensitivity test of knockout mutants for six ketoconazole-upregulated genes in ergosterol biosynthesis revealed that deletion of only sterol C-22 desaturase ERG5 altered sensitivity to azoles: the erg5 mutant was hypersensitive to azoles but had no obvious defects in growth and development. The erg5 mutant accumulated higher levels of ergosta 5,7-dienol relative to the wild type but its levels of 14α-methylated sterols were similar to the wild type. ERG5 homologs are highly conserved in fungal kingdom. Deletion of Fusarium verticillioides erg5 also increased ketoconazole sensitivity, suggesting that the roles of ERG5 homologs in azole resistance are highly conserved among different fungal species, and inhibition of ERG5 could reduce the usage of azoles and thus provide a new target for drug design.
is the second most common cause of invasive candidiasis and is widely known to have reduced susceptibility to fluconazole relative to many other spp. Upc2A is a transcription factor that regulates ergosterol biosynthesis gene expression under conditions of sterol stress such as azole drug treatment or hypoxia. Through an microevolution experiment, we found that loss-of-function mutants of the ATF/CREB transcription factor suppresses the fluconazole hyper-susceptibility of the ∆ mutant.
Cholesterol is a fundamental component of cellular membranes, and its organization, distribution, and recycling are tightly regulated. Cholesterol can form, together with other lipids and proteins, membrane nanodomains, which play important roles in membrane trafficking, the spatiotemporal organization of signal transduction, or the modulation of plasma membrane transporters, among others. Not surprisingly then, the misregulation of cholesterol biosynthetic and transport pathways has been related to numerous diseases, including neurodegenerative and metabolic disorders.
Grupo de Investigación en Química Orgánica y Biomédica, Programa de Química, Facultad de Ciencias Básicas, Universidad Del Atlántico, A.A.1890, Barranquilla, Colombia.
Drug-resistant fungal infections pose a formidable challenge in healthcare, attributed to ergosterol production as a key mechanism of resistance. It is therefore imperative to target this pathway for effective therapeutic interventions. In this study, we have analyzed the binding mode of twelve quinoline derivatives known to be effective against various Candida species, Microsporum gypseum, and Cryptococcus neoformans.
The Lanzhou lily bulbs are often vulnerable to postharvest infections by pathogenic fungi, leading to lily bulb rot. This study investigated the ability of volatile organic compounds (VOCs) produced by Stenotrophomonas geniculata J-0 to control the highly pathogenic fungus Fusarium oxysporum BH-7 in postharvest Lanzhou lily bulbs. VOCs of S.
Laboratório de Bioquímica e Imunologia das Micoses, Departamento de Microbiologia e Parasitologia, Universidade Federal Fluminense, Niterói, Rio de Janeiro, Brazil.
Unlabelled: is an emerging fungal pathogen notable for its resistance to multiple antifungals and ability to survive in various environments. Understanding the interactions between and environmental protozoa, such as could provide insights into fungal adaptability and pathogenicity. Two isolates (MMC1 and MMC2) were co-cultured with to examine interaction dynamics, survival, stress responses, growth, virulence, biofilm formation, and antifungal susceptibility.
