Interaction of Candida albicans Biofilms with Antifungals: Transcriptional Response and Binding of Antifungals to Beta-Glucans
| Autor: | Christophe d'Enfert, Tristan Rossignol, Govindsamy Vediyappan |
|---|---|
| Přispěvatelé: | Biologie et Pathogénicité fongiques (BPF), Institut National de la Recherche Agronomique (INRA)-Institut Pasteur [Paris] (IP), We are grateful to Caroline Proux and Jean-Yves Coppé at the PF2 Platform of Pasteur Genopole Ile-de-France for help with microarray experiments. Caspofungin was kindly provided by Merck & Co. Fluconazole was kindly provided by Pfizer Inc.This work was supported by a grant from the European Commission to C.D. (EURESFUN, LSHM-CT-2005-518199). G.V. was the recipient of a postdoctoral fellowship in the framework of the EURESFUN Consortium. T.R. was the recipient of a postdoctoral fellowship in the framework of the NPARI Consortium (LSHE-CT-2006-037692)., Biologie et Pathogénicité fongiques, Institut National de la Recherche Agronomique (INRA)-Institut Pasteur [Paris], Institut Pasteur [Paris]-Institut National de la Recherche Agronomique (INRA) |
| Rok vydání: | 2010 |
| Předmět: |
MESH: Extracellular Matrix Proteins
Antifungal Agents beta-Glucans Transcription Genetic MESH: Membrane Glycoproteins Extracellular matrix Echinocandins chemistry.chemical_compound MESH: Lipopeptides Caspofungin Gene Expression Regulation Fungal Candida albicans Gene expression Pharmacology (medical) Luciferases Fluconazole [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology Extracellular Matrix Proteins 0303 health sciences Membrane Glycoproteins MESH: beta-Glucans Corpus albicans Infectious Diseases MESH: Fluconazole MESH: Fungal Proteins MESH: Gene Expression Regulation Fungal medicine.drug MESH: Biofilms Biology MESH: Drug Resistance Fungal Microbiology Fungal Proteins MESH: Gene Expression Profiling Lipopeptides 03 medical and health sciences Drug Resistance Fungal Amphotericin B MESH: Amphotericin B medicine Mechanisms of Action: Physiological Effects 030304 developmental biology Pharmacology 030306 microbiology MESH: Transcription Genetic MESH: Candida albicans MESH: Echinocandins Gene Expression Profiling Biofilm biochemical phenomena metabolism and nutrition MESH: Antifungal Agents biology.organism_classification In vitro chemistry Biofilms MESH: Luciferases |
| Zdroj: | Antimicrobial Agents and Chemotherapy Antimicrobial Agents and Chemotherapy, 2010, 54 (5), pp.2096-111. ⟨10.1128/AAC.01638-09⟩ Antimicrobial Agents and Chemotherapy, American Society for Microbiology, 2010, 54 (5), pp.2096-111. ⟨10.1128/AAC.01638-09⟩ |
| ISSN: | 1098-6596 0066-4804 |
| DOI: | 10.1128/aac.01638-09 |
| Popis: | Candida albicans can form biofilms that exhibit elevated intrinsic resistance to various antifungal agents, in particular azoles and polyenes. The molecular mechanisms involved in the antifungal resistance of biofilms remain poorly understood. We have used transcript profiling to explore the early transcriptional responses of mature C. albicans biofilms exposed to various antifungal agents. Mature C. albicans biofilms grown under continuous flow were exposed for as long as 2 h to concentrations of fluconazole (FLU), amphotericin B (AMB), and caspofungin (CAS) that, while lethal for planktonic cells, were not lethal for biofilms. Interestingly, FLU-exposed biofilms showed no significant changes in gene expression over the course of the experiment. In AMB-exposed biofilms, 2.7% of the genes showed altered expression, while in CAS-exposed biofilms, 13.0% of the genes had their expression modified. In particular, exposure to CAS resulted in the upregulation of hypha-specific genes known to play a role in biofilm formation, such as ALS3 and HWP1 . There was little overlap between AMB- or CAS-responsive genes in biofilms and those that have been identified as AMB, FLU, or CAS responsive in C. albicans planktonic cultures. These results suggested that the resistance of C. albicans biofilms to azoles or polyenes was due not to the activation of specific mechanisms in response to exposure to these antifungals but rather to the intrinsic properties of the mature biofilms. In this regard, our study led us to observe that AMB physically bound C. albicans biofilms and beta-glucans, which have been proposed to be major constituents of the biofilm extracellular matrix and to prevent azoles from reaching biofilm cells. Thus, enhanced extracellular matrix or beta-glucan synthesis during biofilm growth might prevent antifungals, such as azoles and polyenes, from reaching biofilm cells, thus limiting their toxicity to these cells and the associated transcriptional responses. |
| Databáze: | OpenAIRE |
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