Invited seminar- Development and use of Candida albicans in vivo systems and novel tools to prevent biofilm formation

February 19, 2014

Dominique Sanglard

Prof. Dominique Sanglard and Prof. Patrick van Dijck 

Prof.Van Dijck

SUMMARY

Candida albicans is a major human fungal pathogen causing mucosal and deep tissue infections of which the majority is associated with biofilm formation on medical implants. Biofilms have a huge impact on public health, as fungal biofilms are highly resistant against most antimycotics. We have developed a subcutaneous biofilm model system in rats (Řičicová et al., 2010) and used this model to test the effect of echinocandin drugs (micafungin, caspofungin and anidulafungin) on C. albicans biofilm formation (Kucharíková et al., 2013). In this model, evaluation of biofilm development is limited to ex vivo analyses, requiring host sacrifice, which excludes longitudinal monitoring of dynamic processes during biofilm formation in the live host. To overcome this limitation, we have developed a non-invasive, dynamic imaging approach using bioluminescence, where the amount of biofilm (and even the morphology of the cells) can be followed over time in the same animal (Vande Velde et al., 2014a, 2014b). This method has immediate applications for the screening and validation of antimycotics under in vivo conditions, for studying host-biofilm interactions in different transgenic mouse models and the contribution of specific genes for biofilm formation.

In an effort to develop new antifungals, we are developing a novel technology to inactivate a protein of choice by inducing its aggregation. To achieve this, small peptides originating from the target protein, that are identified based on their high tendency to induce cross b-aggregation are added to C. albicans cells and aggregate the target protein. We have used Als3 as an example. Als3 peptides are shown to strongly reduce adhesion, biofilm formation and invasion into epithelial cells, all characteristics of an als3 mutant. In addition, using FACS staining or Atomic Force Microscopy, we show that the amount of Als3 on the surface of hyphal cells is strongly reduced in the presence of the specific peptide. Some preliminary data on mixed (bacterial-fungal) biofilms will also be presented.

ROUND-TABLE DISCUSSION February 19^th, 2014 from 13:15-15:15

Location: CHUV-Institute of Microbiology, Bugnon 48. Room 502

Organizer: Prof. Patrick Van Dijck

Papers for reading

Beaussart, A., Alsteens, D., El-Kirat-Chatel, S., Lipke, P. N., Kucharíková, S., Van Dijck, P., & Dufrêne, Y. F. (2012). Single-Molecule Imaging and Functional Analysis of Als Adhesins and Mannans during Candida albicans Morphogenesis. ACS Nano, 121112092323001. doi:10.1021/nn304505s

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Beaussart, A., Herman, P., El-Kirat-Chatel, S., Lipke, P. N., Kucharíková, S., Van Dijck, P., & Dufrêne, Y. F. (2013). Single-cell force spectroscopy of the medically important Staphylococcus epidermidis–Candida albicans interaction. Nanoscale, 5(22), 10894. doi:10.1039/c3nr03272h

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Vande Velde, G., Kucharíková, S., Schrevens, S., Himmelreich, U., & Van Dijck, P. (2013). Towards non-invasive monitoring of pathogen-host interactions during Candida albicansbiofilm formation using in vivobioluminescence. Cellular Microbiology, 16(1), 115–130. doi:10.1111/cmi.12184

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CHUV-IMUL-502

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