<i>Cryptococcus neoformans</i>
            Resistance to Echinocandins: (1,3)β-Glucan Synthase Activity Is Sensitive to Echinocandins

Maligie, Marybeth A.; Selitrennikoff, Claude P.

doi:10.1128/aac.49.7.2851-2856.2005

Cited by 154 publications

(122 citation statements)

References 49 publications

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“…and members of the Zygomycete family are resistant to echinocandin drugs (MIC> 16 μg/ml) (Pfaller et al, 1998;Singh et al, 2005). The mechanism of this inherent resistance is not related to target insensitivity, as glucan synthase activity from Cryptococcus and several moulds were strongly inhibited by caspofungin in in vitro assays (Maligie et al, 2005;Kahn et al, 2006). However, it should be noted that like Aspergillus spp., some moulds (Curvularia, Alternaria, Acremonium, Trichoderma) showed sensitivity to caspofungin in minimum effective concentration (MEC) assays (Kurtz et al v 1994) using morphological endpoints (Kahn et al 2006).…”

Section: Mechanism Of Inherent Resistance In Non-candida Spp Remainsmentioning

confidence: 99%

“…However, it should be noted that like Aspergillus spp., some moulds (Curvularia, Alternaria, Acremonium, Trichoderma) showed sensitivity to caspofungin in minimum effective concentration (MEC) assays (Kurtz et al v 1994) using morphological endpoints (Kahn et al 2006). Nevertheless, organisms like Cryptococcus are effectively resistant, despite the fact that glucan synthase is fully inhibited by drug (Maligie et al, 2005), indicating the presence of an alternative mechanism impendent of Fks1. As the echinocandins require transport into the cell to their site of action, the surface properties of fungi may contribute to resistance.…”

Section: Mechanism Of Inherent Resistance In Non-candida Spp Remainsmentioning

confidence: 99%

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Resistance to echinocandin-class antifungal drugs

Perlin¹

2007

Drug Resistance Updates

451

400

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Invasive fungal infections cause morbidity and mortality in severely ill patients, and limited drug classes restrict treatment choices. The echinocandins drugs are the first new class of antifungal compounds that target the fungal cell wall by blocking β-1,3-D-glucan synthase. Elevated MIC values with occasional treatment failure have been reported for strains of Candida. Yet, an uncertain correlation exists between clinical failure and elevated MIC values for the echinocandin drugs. Fungi display several adaptive physiological mechanisms that result in elevated MIC values. However, resistance to echinocandin drugs among clinical isolates is associated with amino acid substitutions in two "hot-spot" regions of Fks1, the major subunit of glucan synthase. The mutations, yielding highly elevated MIC values, are genetically dominant and confer cross-resistance to all echinocandin drugs. Prominent Fks1 mutations decrease the sensitivity of glucan synthase for drug by one thousand-fold or more, and strains harboring such mutations may require a concomitant increase in drug to reduce fungal organ burdens in animal infection models. The Fks1-mediated resistance mechanism is conserved in a wide variety of Candida spp. and can account for intrinsic reduced susceptibility of certain species. Fks1 mutations confer resistance in both yeasts and moulds suggesting that this mechanism is pervasive in the fungal kingdom.

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Section: Mechanism Of Inherent Resistance In Non-candida Spp Remainsmentioning

confidence: 99%

Section: Mechanism Of Inherent Resistance In Non-candida Spp Remainsmentioning

confidence: 99%

Resistance to echinocandin-class antifungal drugs

Perlin¹

2007

Drug Resistance Updates

451

400

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“…Although echinocandins are commonly used in the treatment of fungal infections due to their activity against the β-1–3-D-glucan cell wall, Cryptococcus species are intrinsically resistant to this class of medications without a known etiology [4,8]. C. laurentii has added resistance due to biofilm formation, which prevents adequate antibiotic penetration [9].…”

Section: Discussionmentioning

confidence: 99%

Perspectives on non-neoformanscryptococcal opportunistic infections

Smith¹,

Sehring²,

Chambers³

et al. 2017

Journal of Community Hospital Internal Medicine Perspectives

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Non-neoformans Cryptococcus species, including C. laurentii and C. albidus, have historically been classified as exclusively saprophytic. However, recent studies have increasingly implicated these organisms as the causative agent of opportunistic infections in humans. Herein, the case is presented of C. laurentii meningitis in a critically ill patient receiving corticosteroids. C. laurentii has been implicated in an additional 18 cases of opportunistic infection, predominantly of the skin, bloodstream, and central nervous system. The most clinically significant risk factors for non-neoformans cryptococcal infections include: impaired cell-mediated immunity, recent corticosteroid use, and invasive catheter placement. This article provides a comprehensive review of the clinical relevance, pathogenesis, risk factors, and treatment of non-neoformans Cryptococcus species.

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“…The two fungal genera most commonly targeted are Candida and Aspergillus. This search may seem unrealistic since the organization of cell wall enzymes is species specific, the permeability of the cell wall and associated extracellular matrix to the antifungal drug varies with the fungal species and the sensitivity of the enzymes themselves to the drug is also species-dependent [27]. For example, Candida neoformans glucan synthase is insensitive to caspofungin [28] and echinocandins are not very efficient in treating Zygomycetes.…”

Section: Identifying New Targets and Revisiting Old Targetsmentioning

confidence: 99%