Experimental biofilm-related Candida infections.

Future Microbiol. 2013 Jun;8(6):799-805.

Cirasola D, Sciota R, Vizzini L, Ricucci V, Morace G, Borghi E.

Department of Health Sciences, Università degli Studi di Milano, via A di Rudinì, 8, 20142 Milan, Italy.

Abstract

AIM: We investigated the pathogenic role of biofilm and the therapeutic efficacy of anidulafungin in experimental infections of the wax moth Galleria mellonella by Candida albicans clinical strains.

MATERIALS & METHODS: On the basis of the in vitro propensity to form biofilm, five biofilm-producer (BP) and four nonproducer (NP) C. albicans clinical strains were used in this study. For each strain, we assessed the virulence by infecting G. mellonella larvae and observing survival. Anidulafungin was administered 2 h after yeast inoculum at 0.6 µg, according to the therapeutic dose recommended for humans.

RESULTS: Biofilm-forming ability highly influenced the larva-killing rate. A significant (p < 0.0001) survival decrease was observed in the BP group, with 80% of the infected larvae dying within 72 h. NP isolates did not reach the same killing rate, even at the end of experiments (216 h). Larval survival was enhanced (p < 0.0001) by anidulafungin administration in both groups. Survival rate at 72 h was similar in both groups (BP 78.5% and NP 87.5%); whereas there were still differences at the end of the experiments, with a higher survival in the NP group (75 vs 48%).

CONCLUSION: Our data confirm the pathogenic role of biofilm in C. albicans infections. Its importance was further enhanced by a lack of contribution from extracellular enzymes, detected in both NP and BP strains. In addition, we demonstrated anidulafungin efficacy in treating biofilm-related invasive candidiasis.

PMID: 23701334

 

Supplement:

Microorganisms organized in biofilms are able to evade the host immune response and to impair the activity of antimicrobial drugs. The social impact of nosocomial biofilm-related infections is particularly relevant for patients with life-threatening diseases such cancer or with an inefficient immune system. In this contest, invasive fungal infections, particularly invasive candidiasis, increased in the last decades and are still associated with a high mortality rate. To study the potential efficacy of anidulafungin in fighting biofilm-related infections, we induced systemic Candida albicans infections in the Galleria mellonella experimental model. This model has the advantage to analyze both the virulence factor and the therapeutic power of a drug, overcoming the problems of the use of mammals as the need of an animal facility, restriction on number of animals used, regulatory requirements, costs and ethical issues.

The results of this study highlight how the propensity to form biofilms is an important virulent trait favoring the progression of the infection to a fatal outcome. This is particularly evident in observing the survival of the larvae infected with strains of biofilm producing and non-producing C. albicans. The innovative aspect of the study, in our opinion, can be correlated to the results obtained using the anidulafungin, a commercial drug, to treat proven biofilm-related infections in an in vivo experimental model. Although limited by inoculation of a single dose of the drug, it was possible to show a significant decrease in mortality in larvae infected with biofilm-producing strains.

The use of the experimental model of G. mellonella opens new horizons to better understand the therapeutic potential of a given drug in fighting severe infections with a high mortality rate as well as to link specific characters of virulence of a pathogen to the severity of the infection. The flexibility of the model also allows studying the contribution of innate immunity in assisting the effectiveness of the therapeutic intervention during severe infections related to a well-defined character of virulence.

We thank Elephtherios Mylonakis and Beth Fuchs (Division of Infectious Diseases, Massachusetts General Hospital, Boston, USA) for their collaboration and support on our work, the editorial staff and reviewers of Future Microbiology for their valuable suggestions and comments on our paper.

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