Abstract
SUMMARYCandida spp. are opportunistic pathogens in humans, and their systemic infections display upwards of 30% mortality in immunocompromised patients. Current mammalian model systems have certain disadvantages in that obtaining results is time consuming owing to the relatively long life spans and these results have low statistical resolution because sample sizes are usually small. We have therefore evaluated the potential of Drosophila melanogaster as an additional model system with which to dissect the host-pathogen interactions that occur during Candida albicans systemic infection. To do this, we monitored the survival of wild-type flies infected with various C. albicans clinical isolates that were previously ranked for murine virulence. From our lifetime data we computed two metrics of virulence for each isolate. These correlated significantly with murine survival, and were also used to group the isolates, and this grouping made relevant predictions regarding their murine virulence. Notably, differences in virulence were not predictably resolvable using immune-deficient spz−/− flies, suggesting that Toll signalling might actually be required to predictably differentiate virulence. Our analysis reveals wild-type D. melanogaster as a sensitive and relevant model system; one that offers immense genetic tractability (having an extensive RNA interference library that enables tissue-specific gene silencing), and that is easy to manipulate and culture. Undoubtedly, it will prove to be a valuable addition to the model systems currently used to study C. albicans infection.
Highlights
Candida albicans is a common diploid, polymorphic fungal organism that often colonises mucosal surfaces in healthy human adults without incidence of disease
Impairment of host defence mechanisms owing to underlying immune deficiencies, HIV infection, prolonged chemotherapy, major surgery or immunosuppressant treatments can predispose individuals to infections ranging from mucocutaneous forms of candidiasis, to systemic infections such as candidaemia and invasive candidiasis (Enoch et al, 2006; Netea et al, 2008)
With the realisation that innate immune responses constitute the prototypical host defence that is conserved in metazoans came the usage of genetically tractable invertebrate model systems, such as Caenorhabditis elegans and Drosophila melanogaster, as more practical alternatives for analysing fungal pathogenesis
Summary
Candida albicans is a common diploid, polymorphic fungal organism that often colonises mucosal surfaces in healthy human adults without incidence of disease. Considering the above, it is highly desirable to develop a relevant model system with which to study the host-pathogen interactions taking place during a Candida infection. This would be one that combines predictive power with genetic tractability, one that is easy to manipulate, and one that is available in large numbers. With the realisation that innate immune responses constitute the prototypical host defence that is conserved in metazoans came the usage of genetically tractable invertebrate model systems, such as Caenorhabditis elegans and Drosophila melanogaster, as more practical alternatives for analysing fungal pathogenesis (for a review, see Mylonakis et al, 2007). The limited studies available were performed using immunedeficient flies
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