Antifungal Efficacy during Candida krusei Infection in Non-Conventional Models Correlates with the Yeast In Vitro Susceptibility Profile

Abstract

The incidence of opportunistic fungal infections has increased in recent decades due to the growing proportion of immunocompromised patients in our society. Candida krusei has been described as a causative agent of disseminated fungal infections in susceptible patients. Although its prevalence remains low among yeast infections (2–5%), its intrinsic resistance to fluconazole makes this yeast important from epidemiologic aspects. Non mammalian organisms are feasible models to study fungal virulence and drug efficacy. In this work we have used the lepidopteran Galleria mellonella and the nematode Caenorhabditis elegans as models to assess antifungal efficacy during infection by C. krusei. This yeast killed G. mellonella at 25, 30 and 37°C and reduced haemocytic density. Infected larvae melanized in a dose-dependent manner. Fluconazole did not protect against C. krusei infection, in contrast to amphotericin B, voriconazole or caspofungin. However, the doses of these antifungals required to obtain larvae protection were always higher during C. krusei infection than during C. albicans infection. Similar results were found in the model host C. elegans. Our work demonstrates that non mammalian models are useful tools to investigate in vivo antifungal efficacy and virulence of C. krusei.

Decreased expression of 14-3-3 inParacoccidioides brasiliensisconfirms its involvement in fungal pathogenesis

“…After the infection, the larvae were incubated in Petri dishes at 37 C for 7 days and checked daily for mortality (based on lack of movement after manipulation with forceps). 85 For evaluating the fungal burden of the different isolates, 5 larvae per group were infected as detailed above and sacrificed at each time point (0, 24 and 48 h). The larvae were homogenized in 1 mL sterile PBS, and the homogenates were plated on BHI agar containing chloramphenicol (30 mg mL ¡1 ) as described by Singulani et al (unpublished data).…”

Galleria mellonellaas a host model to studyAspergillus terreusvirulence and amphotericin B resistance

“…14,15 Of particular importance is the strong correlation to data obtained in murine studies. 16 Insects possess a cellular and humoral innate immune system which bears similarities to innate immune response of vertebrates.…”

“…20 Because their density is not stable, examining changes in haemocyte populations can be used to estimate immune responses to fungal infections or drug treatment. 14,21 The aim of this study was to establish and characterize a simple alternative in vivo model to study infections due to A. terreus. Two ATR isolates and 3 ATS isolates were used to determine differences in virulence potential and survival rates were correlated to physiological attributes and to in vitro AMB susceptibility profile.…”

Lactobacillus acidophilus ATCC 4356 inhibits biofilm formation by C. albicans and attenuates the experimental candidiasis in Galleria mellonella

“…15 In this respect, Galleria mellonella has been found to be an interesting invertebrate model for the study of experimental candidiasis. [16][17][18][19][20][21][22][23] This larvae has a sufficient size for injection of a standard inoculum of the microorganism and its hemolymph contains various types of hemocytes that play an important role in the defense against pathogens. 16,17 In these models, the experiments are conducted at temperatures ranging from 25 to 37 C, conditions that simulate the natural environment of mammalian hosts.…”