Potential Antifungal Targets Based on Glucose Metabolism Pathways of Candida albicans

Abstract

In recent years, fungal infections have become a serious health problem. Candida albicans are considered as the fourth most common isolates associated with approximately 40% mortality in bloodstream infections among hospitalized patients. Due to various limitations of classical antifungals used currently, such as limited kinds of drugs, inevitable toxicities, and high price, there is an urgent need to explore new antifungal agents based on novel targets. Generally, nutrient metabolism is involved with fungal virulence, and glucose is one of the important nutrients in C. albicans. C. albicans can obtain and metabolize glucose through a variety of pathways; in theory, many enzymes in these pathways can be potential targets for developing new antifungal agents, and several studies have confirmed that compounds which interfere with alpha-glucosidase, acid trehalase, trehalose-6-phosphate synthase, class II fructose bisphosphate aldolases, and glucosamine-6-phosphate synthase in these pathways do have antifungal activities. In this review, the glucose metabolism pathways in C. albicans, the potential antifungal targets based on these pathways, and some compounds which have antifungal activities by inhibiting several enzymes in these pathways are summarized. We believe that our review will be helpful to the exploration of new antifungal drugs with novel antifungal targets.

Glucose-Binding of Periplasmic Protein GltB Activates GtrS-GltR Two-Component System in Pseudomonas aeruginosa

“…Glucose is an essential nutrient for the human body, serving as a primary fuel for energy production [ 1 ]. Many studies have also suggested that pathogens can exploit glucose as either a nutrient or a signal molecule that induces virulence functions [ 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 ]. Indeed, glucose acquisition is essential for the full virulence potential of pathogenic bacteria [ 11 , 12 ] including Pseudomonas aeruginosa , a major cause of nosocomial infection as well as infection in hosts with compromised defenses [ 13 , 14 ].…”

Trehalose Phosphate Synthase Complex-Mediated Regulation of Trehalose 6-Phosphate Homeostasis Is Critical for Development and Pathogenesis in Magnaporthe oryzae

“…5c and d ). Since T6P is an inhibitor of Tps1p, and in plants, T6P serves as a signaling molecule ( 3 , 69 , 70 ), we speculate that the T6P level must reach a threshold to inhibit MoTps1 activity. At a persistent threshold level, spontaneous mutation of MoTPS3 is induced (likely via the T6P signaling), which in turn suppresses MoTps1 activity to reduce the level of T6P.…”

“…It is a structural component of most organisms, including plants, fungi, lichens, algae, bacteria, insects, and invertebrates, but not vertebrates ( 1 , 2 ). Therefore, disruption of the trehalose biosynthesis pathway could be a promising alternative to developing safe and broad-spectrum fungicidal drugs, especially against human-pathogenic fungi ( 2 , 3 ). To date, five different biosynthesis pathways have been established for the synthesis of trehalose, and the trehalose phosphate synthase/trehalose phosphate phosphatase (TPS/TPP) pathway is the most widely distributed trehalose biosynthesis pathway among these organisms.…”

Targeting β-glucan synthase for Mucormycosis “The 'black fungus” maiming Covid patients in India: computational insights

“…Due to clinical limitations of fungicidal agents, high price, inevitable toxicities, and the appearance of drug resistance, the synthesis of effective and safe fungicidal agents based on novel antifungal targets is instantly needed 3 . The key drug molecules which act as inhibitors of β-1,3-glucan biosynthesis have been advocated as potential therapeutic agents for treating fungal infections 4 . It is a glucosyl-transferase enzyme involved in the generation of beta-glucan in fungi which is key component of cell wall construction.…”