Abstract

Objectives: Cryptococcus neoformans is an opportunistic fungus that causes fatal meningoencephalitis especially in AIDS patients. There is an increasing need for discovery of new anti-cryptococcal drugs due to emergence of resistance cases in recent years. In this study, we aim to elucidate the antifungal effect of triclosan against C. neoformans.Methods: Minimal inhibitory concentration (MIC) of triclosan in different C. neoformans strains was first examined. The in vitro interactions between triclosan and two standard anti-fungal drugs (amphotericin B and fluconazole) were further evaluated by microdilution checkerboard assay. Mechanism of triclosan fungicidal activity was then investigated by viewing the cell morphology under transmission electron microscope.Results: We reported that triclosan potently inhibited the growth of C. neoformans. A combination of triclosan with amphotericin B or with fluconazole enhanced their fungicidal effects. Triclosan-treated C. neoformans displayed characteristics such as nuclear chromatin condensation, extensive intracellular vacuolation and mitochondrial swelling, indicating that triclosan triggered apoptosis-like cell death.Conclusion: In summary, our report suggests triclosan as an independent drug or synergent for C. neoformans treatment.

Highlights

  • Infection by Cryptococcus neoformans has become a major cause of mortality following the increased numbers of AIDS patients (Mitchell and Perfect, 1995; Pancharoen et al, 2001) and is estimated to cause approximately 600,000 deaths worldwide annually (Park et al, 2009)

  • To evaluate the antifungal effect of triclosan, 6-mm paper disks impregnated with different concentrations of triclosan (3.125, 6.25, 12.5, 25, 50, and 100 μg) were positioned on a C. neoformans H99 agar plate for an incubation period of 48 h

  • Triclosan was fungicidal against C. neoformans H99, with Minimal inhibitory concentration (MIC)-1 = 3.80 and MIC-1

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Summary

Introduction

Infection by Cryptococcus neoformans has become a major cause of mortality following the increased numbers of AIDS patients (Mitchell and Perfect, 1995; Pancharoen et al, 2001) and is estimated to cause approximately 600,000 deaths worldwide annually (Park et al, 2009). Triclosan “Inhibits” Cryptococcus neoformans because C. neoformans is an opportunistic pathogen which rarely progresses to disease in immune competent individuals. It can result in life-threatening infection in immunosuppressed or immunocompromised patients (Coelho et al, 2014). The widespread use of anti-microbial drugs in the treatment of fungal infection has led to the global emergence of resistant fungal strains. Numerous fungal pathogens including C. neoformans have demonstrated increasing resistance to common antifungal drugs such as amphotericin B and fluconazole (Perfect and Cox, 1999). A recent global study of nearly three thousand C. neoformans isolates shows that >11% of the isolates are resistant to fluconazole (Pfaller et al, 2009). Combinational usage of fluconazole plus amphotericin B adds benefit in candidemia treatment (Odds, 2003a)

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