A Mouse Model for Candida glabrata Hematogenous Disseminated Infection Starting from the Gut: Evaluation of Strains with Different Adhesion Properties

Abstract

Adhesion to digestive mucosa is considered a crucial first step in the pathogenicity of invasive Candida infections. Candida glabrata disseminated infections predominantly start from the gut. A mouse model of disseminated infection starting from the gut was set up. Hematogenous dissemination was obtained after a low-protein diet followed by a regimen of cyclophosphamide-methotrexate and an oral inoculation of the yeasts via the drinking water. The liver was the first organ infected (day 7 post-infection), and lethality was 100% at day 21 post-infection. This new mouse model was used to compare the mortality rate and fungal burden in deep organs induced by 5 strains exhibiting different levels of adhesion to enterocyte Caco-2 cells, as determined in a test on 36 C. glabrata strains. In this model, no statistical difference of lethality was demonstrated between the strains, and fungal burden varied in kidneys and lungs but without correlation with the level of adhesion to enterocytes. Further studies using the model developed here allow analysis of the crossing of the digestive mucosa by yeasts, and help relate this to yet-poorly understood adhesion phenotypes.

Virulence assessment of six major pathogenic Candida species in the mouse model of invasive candidiasis caused by fungal translocation

“…In order to mimic these pathological aspects, we utilised cyclophosphamide to induce neutropenia 12 , along with enrofloxacin and vancomycin to reduce endogenous murine gastrointestinal bacteria. We also fed the mice low protein diets, which, as previously reported, favour the implantation of C. albicans and C. glabrata in the gut 9,13 . In our model, the liver served as a preferential organ for infection because C. albicans invaded into the gut mucosa and liver before being disseminated to the kidneys (Figs.…”

Combination of Estrogen and Immunosuppressive Agents to Establish a Mouse Model of Candidiasis with Concurrent Oral and Vaginal Mucosal Infection

“…Thus, cortisone was also dosed at 225 mg/kg in this study to avoid an ineffective dose reaction. CTX is one of the more popular immunosuppressors and had been reported to induce neutropenia in establishment of infectious models with a number of fungi, such as Aspergillus fumigatus and Candida glabrata [26,27].…”

“…Here, we chose 100 mg/kg CTX twice a week based on both the literature [26,27] and our preliminary investigation (data not shown). With this dose, CTX can induce prominent oral candidiasis, but the fungal burden of vaginal tissue is at least 10 times lower than group of prednisolone in ICR mice.…”

Candida glabrata: a deadly companion?

“…Subsequent dissemination in the bloodstream will occur if the mucosal barrier is fragile and/or the local immune system deficient, and colonization will appear first in the liver and kidneys, then in the lungs (Atanasova et al ., ). An important factor, which then contributes to invasive success, is the interaction with the immune system.…”