Animal Models for Candidiasis

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unit 19.6

Candidiasis is a disease of immunocompromised patients and Candida albicans is the most frequent causative agent of this mycosis. The fungus lives as a commensal in the genital and gastrointestinal (GI) tracts of healthy humans. Candidiasis encompasses a wide spectrum of clinical diseases that range from acute or chronic localized mucocutaneous infections to life-threatening disseminated disease. Endogenous Candida organisms in the GI tract appear to be the most important source for dissemination of the opportunistic pathogen; hence, candidal colonization of the GI tract is a prerequisite for the development of invasive candidiasis. A variety of underlying conditions is believed to account for susceptibility to mucosal and disseminated C. albicans infections and determines both the severity and characteristics of the associated pathology. These include an overgrowth of the fungus caused by prolonged use of broad-spectrum antibiotics, disruption of the GI barrier resulting from the effect of cytotoxic drugs or hypotension, and congenital or iatrogenic immunosuppression resulting from neutropenia or TH cell dysregulation.

Animal models of candidiasis have been widely used to evaluate the therapeutic efficacy of antifungal agents and various immunomodulators as well as to explore events of mucosal colonization and invasion by the fungus under conditions that simulate the transition from asymptomatic colonization to symptomatic infection in humans. These models include the use of rodents, in particular rats and mice, and occasionally rabbits. With the exception of the vaginal Candida infection model in which the mouse and rat are commonly used, GI and disseminated candidiasis have been studied mainly in inbred strains of mice of different haplotypes. C. albicans is not a component of the indigenous microbial population of the rodent mucosae, and colonization by the fungus is apparently inhibited by the host's innate defenses and mucosal barriers as well as by competition between the yeast and existing microbial flora. However, a number of experimental manipulations have been devised to obtain experimental models of infection closely mimicking human infections.

As little is known about the yeast/host interaction in Candida species other than C. albicans, this unit details the materials and experimental procedures required for development of experimental C. albicans infections, such as GI and disseminated infections in infant Swiss White mice (see Basic Protocol 1) and in adult immunocompromised BALB/c mice (see Alternate Protocol 1), primary acute disseminated infection in BALB/c and DBA/2 mice (see Basic Protocol 2), and vaginal infection in CBA/J mice (see Basic Protocol 3) and in Wistar rats (see Alternate Protocol 2). Detailed materials and methods for C. albicans growth and detection are also described (see Support Protocols 1 to 3). The reader may wish to consult the literature for details regarding modifications of the specified protocols in different mouse and rats strains (see Commentary for additional discussion).

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