Browsing by Author "Madaan, Kashish"

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    Emerging Role of Sphingolipids in Amphotericin B Drug Resistance
    (Mary Ann Liebert Inc., 2023-06-16T00:00:00) Madaan, Kashish; Bari, Vinay Kumar
    Invasive fungal infections in humans are common in people with compromised immune systems and are difficult to treat, resulting in high mortality. Amphotericin B (AmB) is one of the main antifungal drugs available to treat these infections. AmB binds with plasma membrane ergosterol, causing leakage of cellular ions and promoting cell death. The increasing use of available antifungal drugs to combat pathogenic fungal infections has led to the development of drug resistance. AmB resistance is not very common and is usually caused by changes in the amount or type of ergosterol or changes in the cell wall. Intrinsic AmB resistance occurs in the absence of AmB exposure, whereas acquired AmB resistance can develop during treatment. However, clinical resistance arises due to treatment failure with AmB and depends on multiple factors such as the pharmacokinetics of AmB, infectious fungal species, and host immune status. Candida albicans is a common opportunistic pathogen that can cause superficial infections of the skin and mucosal surfaces, thrush, to life-Threatening systemic or invasive infections. In addition, immunocompromised individuals are more susceptible to systemic infections caused by Candida, Aspergillus, and Cryptococcus. Several antifungal drugs with different modes of action are used to treat systemic to invasive fungal infections and are approved for clinical use in the treatment of fungal diseases. However, C. albicans can develop a variety of defenses against antifungal medications. In fungi, plasma membrane sphingolipid molecules could interact with ergosterol, which can lead to the alteration of drug susceptibilities such as AmB. In this review, we mainly summarize the role of sphingolipid molecules and their regulators in AmB resistance. � Copyright 2023, Mary Ann Liebert, Inc., publishers 2023.