Abstract
The substantial morbidity and mortality associated with invasive fungal infections constitute undisputed tokens of their severity. The continued expansion of susceptible population groups (such as immunocompromised individuals, patients undergoing extensive surgery, and those hospitalized with serious underlying diseases especially in the intensive care unit) and the limitations of current antifungal agents due to toxicity issues or to the development of resistance, mandate the development of novel antifungal drugs. Currently, drug discovery is transitioning from the traditional in vitro large-scale screens of chemical libraries to more complex bioassays, including in vivo studies on whole animals; invertebrates, such as Caenorhabditis elegans, are thus gaining momentum as screening tools. Key pathogenesis features of fungal infections, including filament formation, are expressed in certain invertebrate and mammalian hosts; among the various potential hosts, C. elegans provides an attractive platform both for the study of host-pathogen interactions and the identification of new antifungal agents. Advantages of compound screening in this facile, relatively inexpensive and not as ethically challenged whole-animal context, include the simultaneous assessment of antifungal efficacy and toxicity that could result in the identification of compounds with distinct mechanisms of action, for example by promoting host immune responses or by impeding fungal virulence factors. With the recent advent of using predictive models to screen for compounds with improved chances of bioavailability in the nematode a priori, high-throughput screening of chemical libraries using the C. elegans-C. albicans antifungal discovery assay holds even greater promise for the identification of novel antifungal agents in the near future.
Keywords: Invertebrate model hosts, non-mammalian animal models, systemic mycoses, Candida albicans, high-throughput in vivo screening, drug bioaccumulation model, Caenorhabditis elegans, mycoses, deoxycholate, echinocandins, triazoles, caspofungin, anidulafungin, Escherichia coli, orthologues, antimycotics, hermaphroditism, fluorescence, fluoroquinolone, enoxacin, antitrypsin, saponin
Current Pharmaceutical Design
Title: Caenorhabditis elegans-based Model Systems for Antifungal Drug Discovery
Volume: 17 Issue: 13
Author(s): Cleo G. Anastassopoulou, Beth Burgwyn Fuchs and Eleftherios Mylonakis
Affiliation:
Keywords: Invertebrate model hosts, non-mammalian animal models, systemic mycoses, Candida albicans, high-throughput in vivo screening, drug bioaccumulation model, Caenorhabditis elegans, mycoses, deoxycholate, echinocandins, triazoles, caspofungin, anidulafungin, Escherichia coli, orthologues, antimycotics, hermaphroditism, fluorescence, fluoroquinolone, enoxacin, antitrypsin, saponin
Abstract: The substantial morbidity and mortality associated with invasive fungal infections constitute undisputed tokens of their severity. The continued expansion of susceptible population groups (such as immunocompromised individuals, patients undergoing extensive surgery, and those hospitalized with serious underlying diseases especially in the intensive care unit) and the limitations of current antifungal agents due to toxicity issues or to the development of resistance, mandate the development of novel antifungal drugs. Currently, drug discovery is transitioning from the traditional in vitro large-scale screens of chemical libraries to more complex bioassays, including in vivo studies on whole animals; invertebrates, such as Caenorhabditis elegans, are thus gaining momentum as screening tools. Key pathogenesis features of fungal infections, including filament formation, are expressed in certain invertebrate and mammalian hosts; among the various potential hosts, C. elegans provides an attractive platform both for the study of host-pathogen interactions and the identification of new antifungal agents. Advantages of compound screening in this facile, relatively inexpensive and not as ethically challenged whole-animal context, include the simultaneous assessment of antifungal efficacy and toxicity that could result in the identification of compounds with distinct mechanisms of action, for example by promoting host immune responses or by impeding fungal virulence factors. With the recent advent of using predictive models to screen for compounds with improved chances of bioavailability in the nematode a priori, high-throughput screening of chemical libraries using the C. elegans-C. albicans antifungal discovery assay holds even greater promise for the identification of novel antifungal agents in the near future.
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Cite this article as:
G. Anastassopoulou Cleo, Burgwyn Fuchs Beth and Mylonakis Eleftherios, Caenorhabditis elegans-based Model Systems for Antifungal Drug Discovery, Current Pharmaceutical Design 2011; 17 (13) . https://dx.doi.org/10.2174/138161211795703753
DOI https://dx.doi.org/10.2174/138161211795703753 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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