Miconazole resistance in fungal biofilms : a molecular point of view

The interest in fungal biofilm formation and in the resistance of fungal biofilms against antimicrobial agents has increased due to the expanding problem of biofilm-related infections. In this doctoral research the activity of miconazole against biofilms of Candida species has been investigated. Furthermore, we have focused on the molecular mechanisms involved in fungal biofilm formation and in resistance to miconazole. The data showed that miconazole has a fungicidal activity against Candida spp. biofilms. The exact mechanism leading to cell death could not be elucidated, and possibly includes other mechanisms than increased ROS levels. Notwithstanding the fungicidal activity of miconazole against Candida spp. biofilms, we noticed a resistant fraction (1% - 10%) of sessile cells that was able to survive a high dose of miconazole. The molecular mechanisms of biofilm formation and the resistance to miconazole were unraveled by screening a S. cerevisiae deletion mutant bank. The results of the screening highlighted the multi-factorial complexity of biofilm formation and resistance. An in depth analysis of the results revealed that two major biological processes play an important role in S. cerevisiae biofilm formation and the susceptibility to miconazole, i.e. the organization of two types of organelles, the mitochondria and the peroxisomes. Furthermore, we demonstrated that phytosphingosine-1-phosphate has a protective effect against miconazole treatment. Experiments in C. albicans indicated that this intermediate of the sphingolipid biosynthesis acts as a signaling molecule enhancing the export of miconazole. This doctoral research showed that miconazole has a fungicidal activity against Candida spp. biofilms and unraveled the mechanisms involved in fungal biofilm formation and resistance to miconazole.

Grantor dc:publisher

Ghent University. Faculty of Pharmaceutical Sciences

Year dc:date

2013

Author dc:creator

• Vandenbosch, Davy

Contributors dc:contributor

• Coenye, Tom
• Nelis, Hans

• Biology and Life Sciences

Statement dc:rights

• info:eu-repo/semantics/openAccess

Language dc:language

eng

Identifier

https://biblio.ugent.be/publication/3259934
https://biblio.ugent.be/publication/3259934/file/4336583

OAI identifier oai:identifier

oai:archive.ugent.be:3259934