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.
Highlights
In recent years, invasive fungal infections have been increasing all the time due to the widespread use of immunosuppressants and antibiotics, the increase of patients with AIDS, and the development of organ transplantation (Van Ende et al, 2019)
We described the various potential antifungal targets which are proved to be related to C. albicans virulence in these glucose metabolism pathways, and several compounds which have antifungal activities based on alpha-glucosidase, acid trehalase, trehalose-6-phosphate synthase, isocitrate lyase, malate synthase, enolase, class II fructose bisphosphate aldolases, and glucosamine-6-phosphate synthase
The sensitivity to macrophage phagocytosis of tps2 /tps2 strain is quite different compared with wildtype strains, and the results demonstrated that C. albicans strain which lacks the TPS2 gene is more susceptible to macrophage engulfment than wild-type strains (Martinez-Esparza et al, 2009)
Summary
Invasive fungal infections have been increasing all the time due to the widespread use of immunosuppressants and antibiotics, the increase of patients with AIDS, and the development of organ transplantation (Van Ende et al, 2019). We are primarily focusing on the antifungal activities of some compounds with the potential antifungal targets on fungal specific enzymes in glucose metabolism pathways.
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