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.

Highlights

  • Fungal infections have emerged worldwide due to a growing population of immunosuppressed patients, including patients with cancer, AIDS, solid-organ and hematopoietic stem cell transplant recipients, premature neonates, and patients recovering from major surgery [1,2,3,4,5]

  • Candida krusei killed G. mellonella in a dose dependant manner We first investigated if C. krusei killed G. mellonella

  • Our results showed that G. mellonella is susceptible to C. krusei infection (Figure 1A)

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Summary

Introduction

Fungal infections have emerged worldwide due to a growing population of immunosuppressed patients, including patients with cancer, AIDS, solid-organ and hematopoietic stem cell transplant recipients, premature neonates, and patients recovering from major surgery [1,2,3,4,5]. These infections have significant morbidity and mortality rates and are difficult to prevent, diagnose and treat [6,7,8]. There are some species that are intrinsically resistant or have reduced susceptibility to antifungals. The massive use of antifungals in prophylaxis, such as fluconazole, has facilitated the selection of pathogenic fungi resistant to these agents [16,17,18,19]

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