Non-Lethal Candida Albicans CPH1/CPH1 EFG1/EFG1 Transcription Factor Mutant Establishing Restricted Zone of Infection in a Mouse Model of Systemic Infection

Abstract

The cph1/cph1 efg1/efg1 Candida albicans mutant cells were non-lethal in a mouse model of systemic infection. We investigated in vivo proliferation and invasion of C. albicans cells in infected mice to elucidate the interaction between the host and the pathogen. Homogenates of kidneys from the mice infected with the wild-type and the mutant C. albicans cells yielded a mean of 2.1 × 107 CFU/g and 2.2 × 106 CFU/g, respectively. The kidneys from the mice infected with the wild-type cells showed extensive renal cortical necrosis associated with neutrophilic infiltration. There were also wild-type hyphal cells present in abundance. Hence, tubular necrosis leading to renal failure in the mice may be the cause of death. Although the cph1/cph1 efg1/efg1 mutant cells were not lethal, they were capable of establishing restricted zones of infection and colonization near the renal pelvis instead of simply being cleared by the immune system in mice.

Zebrafish as a Model Host for Candida albicans Infection

“…7), and this finding is consistent with the results of previous studies of mice (9,23,36). In contrast, WYZ12.2 (hgc1/hgc1) did not form true hyphae within zebrafish; instead, the cells had a pseudohyphal morphology that included short tubes and multiple branches, while hyphal morphology was observed for the reconstituted strain containing HGC1 (Fig.…”

“…Similar results have been obtained with the mouse model and in other in vitro studies. In addition, all of the results indicate that the reduced virulence of HLC54 is complicated and not caused simply by defects in morphogenesis (9,29,36). In contrast to HLC54, the HGC1 deletion strain did not form true hyphae during C. albicans infection in zebrafish, and it did not directly influence the expression of several of the downstream genes regulated by CPH1 and EFG1.…”

“…All of these examples indicate that the zebrafish model is a useful tool for studying infectious disease, and our study expanded its use to fungal pathogens. Several in vivo studies of mammal models have indicated that deletion of CPH1 and EFG1 can restrict the dimorphic transition of C. albicans under many hypha-inducing conditions but that a corresponding double mutant strain can transition into the filamentous form in the model organism's kidney or tongue (9,23,36). To focus on the morphogenic transition and other aspects of C. albicans pathogenesis, we introduced two hypha-defective mutant strains, HLC54 (cph1/efg1) and WYZ12.2 (hgc1), and a noninvasive clinical isolate, ATCC 10231, into zebrafish.…”

A murine model for catheter-associated candiduria

“…So far, candiduria has been investigated predominantly in mice, rats and rabbits (Chen et al, 2006;Hurley & Winner, 1963;Khan & Owais, 2006;Navarro et al, 1994;Nishiksawa et al, 1997;Silva et al, 2007;Tarry et al, 1989;Toth & Hughes, 2006). Experiments in larger animals are more costly, cannot be done with large numbers and genetic-knockout strains are limited or do not exist.…”

Involvement of NK Cells against Tumors and Parasites

“…NK cells appear to be activated mainly in an indirect manner by macrophages or dendritic cell-derived cytokines. On the other hand, T. cruzi glycolipids have been reported to directly stimulate murine NK cell activity (30)(31)(32)(33)(34).…”