title: Effect of Antifungal Treatment in a Diet-Based Murine Model of Disseminated Candidiasis Acquired via the Gastrointestinal Tract.
abstract: Candida albicans, normally found as a commensal in the gut, is a major human fungal pathogen responsible for both mucosal and systemic infections in a wide variety of immunocompromised individuals, including cancer patients and organ transplant recipients. The gastrointestinal tract represents a major portal of entry for the establishment of disseminated candidiasis in many of these individuals. Here we report the development of a diet-based mouse model for disseminated candidiasis acquired via the gastrointestinal tract. Using this model, as well as an appropriate immunosuppression regimen, we demonstrate that dissemination of C. albicans from the gastrointestinal tract can result in mortality within 30 days postinfection. We also show a significant increase in fungal burden in systemic organs, but not gastrointestinal tract organs, upon immunosuppression. Importantly, we demonstrate that the administration of two widely used antifungals, fluconazole and caspofungin, either pre- or postimmunosuppression, significantly reduces fungal burdens. This model should prove to be of significant value for testing the ability of both established and experimental therapeutics to inhibit C. albicans dissemination from the gastrointestinal tract in an immunocompromised host as well as the subsequent mortality that can result from disseminated candidiasis.
authors: Department of Microbiology, Immunology, and Molecular Genetics, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA kadosh@uthscsa.edu.
authors: David
authors: 0000-0001-7237-8481
authors: D
authors: Kadosh
authors: Department of Medicine, Division of Infectious Diseases, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.|South Texas Veterans Health Care System, San Antonio, Texas, USA.
authors: Laura K
authors: LK
authors: Najvar
authors: Department of Medicine, Division of Infectious Diseases, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.|South Texas Veterans Health Care System, San Antonio, Texas, USA.
authors: Rosie
authors: R
authors: Bocanegra
authors: Department of Medicine, Division of Infectious Diseases, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.
authors: Marcos
authors: M
authors: Olivo
authors: Department of Medicine, Division of Infectious Diseases, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.|South Texas Veterans Health Care System, San Antonio, Texas, USA.
authors: William R
authors: WR
authors: Kirkpatrick
authors: Department of Pathology, Fungus Testing Laboratory, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.
authors: Nathan P
authors: NP
authors: Wiederhold
authors: Department of Medicine, Division of Infectious Diseases, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.|South Texas Veterans Health Care System, San Antonio, Texas, USA.
authors: Thomas F
authors: TF
authors: Patterson
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects* / Q000254:growth & development / Q000472:pathogenicity; D002177:Candidiasis / Q000188:drug therapy* / Q000209:etiology / Q000276:immunology / Q000401:mortality; D000077336:Caspofungin; D015169:Colony Count, Microbial; D003520:Cyclophosphamide / Q000009:adverse effects; D004032:Diet / Q000009:adverse effects*; D004195:Disease Models, Animal; D054714:Echinocandins / Q000494:pharmacology*; D015725:Fluconazole / Q000494:pharmacology*; D041981:Gastrointestinal Tract / Q000187:drug effects / Q000276:immunology / Q000382:microbiology; D006801:Humans; D016867:Immunocompromised Host; D007166:Immunosuppressive Agents / Q000009:adverse effects; D055666:Lipopeptides / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011239:Prednisolone / Q000009:adverse effects / Q000031:analogs & derivatives; D016019:Survival Analysis
chemical_list: D000935:Antifungal Agents; D054714:Echinocandins; D007166:Immunosuppressive Agents; D055666:Lipopeptides; D003520:Cyclophosphamide; D015725:Fluconazole; D011239:Prednisolone; D000077336:Caspofungin; C021322:prednisolone hemisuccinate