This Article Full Text Full Text (PDF) Other Versions of this Article: AAC.01056-06v1 51/2/510    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Nett, J. Articles by Andes, D. Search for Related Content PubMed PubMed Citation Articles by Nett, J. Articles by Andes, D.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, February 2007, p. 510-520, Vol. 51, No. 2
0066-4804/07/$08.00+0     doi:10.1128/AAC.01056-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Putative Role of ß-1,3 Glucans in Candida albicans Biofilm Resistance

Departments of Medicine and Medical Microbiology and Immunology,¹ University of Wisconsin Electron Microscopy Facility, University of Wisconsin, Madison, Wisconsin²

Received 22 August 2006/ Returned for modification 17 October 2006/ Accepted 12 November 2006

Biofilms are microbial communities, embedded in a polymeric matrix, growing attached to a surface. Nearly all device-associated infections involve growth in the biofilm life style. Biofilm communities have characteristic architecture and distinct phenotypic properties. The most clinically important phenotype involves extraordinary resistance to antimicrobial therapy, making biofilm infections very difficulty to cure without device removal. The current studies examine drug resistance in Candida albicans biofilms. Similar to previous reports, we observed marked fluconazole and amphotericin B resistance in a C. albicans biofilm both in vitro and in vivo. We identified biofilm-associated cell wall architectural changes and increased ß-1,3 glucan content in C. albicans cell walls from a biofilm compared to planktonic organisms. Elevated ß-1,3 glucan levels were also found in the surrounding biofilm milieu and as part of the matrix both from in vitro and in vivo biofilm models. We thus investigated the possible contribution of ß-glucans to antimicrobial resistance in Candida albicans biofilms. Initial studies examined the ability of cell wall and cell supernatant from biofilm and planktonic C. albicans to bind fluconazole. The cell walls from both environmental conditions bound fluconazole; however, four- to fivefold more compound was bound to the biofilm cell walls. Culture supernatant from the biofilm, but not planktonic cells, bound a measurable amount of this antifungal agent. We next investigated the effect of enzymatic modification of ß-1,3 glucans on biofilm cell viability and the susceptibility of biofilm cells to fluconazole and amphotericin B. We observed a dose-dependent killing of in vitro biofilm cells in the presence of three different ß-glucanase preparations. These same concentrations had no impact on planktonic cell viability. ß-1,3 Glucanase markedly enhanced the activity of both fluconazole and amphotericin B. These observations were corroborated with an in vivo biofilm model. Exogenous biofilm matrix and commercial ß-1,3 glucan reduced the activity of fluconazole against planktonic C. albicans in vitro. In sum, the current investigation identified glucan changes associated with C. albicans biofilm cells, demonstrated preferential binding of these biofilm cell components to antifungals, and showed a positive impact of the modification of biofilm ß-1,3 glucans on drug susceptibility. These results provide indirect evidence suggesting a role for glucans in biofilm resistance and present a strong rationale for further molecular dissection of this resistance mechanism to identify new drug targets to treat biofilm infections.

Published ahead of print on 27 November 2006.

This article has been cited by other articles:

• Nett, J. E., Guite, K. M., Ringeisen, A., Holoyda, K. A., Andes, D. R. (2008). Reduced Biocide Susceptibility in Candida albicans Biofilms. Antimicrob. Agents Chemother. 52: 3411-3413 [Abstract] [Full Text]  
• Al-Dhaheri, R. S., Douglas, L. J. (2008). Absence of Amphotericin B-Tolerant Persister Cells in Biofilms of Some Candida Species. Antimicrob. Agents Chemother. 52: 1884-1887 [Abstract] [Full Text]  
• Cowen, L. E., Steinbach, W. J. (2008). Stress, Drugs, and Evolution: the Role of Cellular Signaling in Fungal Drug Resistance. Eukaryot Cell 7: 747-764 [Full Text]  
• Angiolella, L., Stringaro, A. R., De Bernardis, F., Posteraro, B., Bonito, M., Toccacieli, L., Torosantucci, A., Colone, M., Sanguinetti, M., Cassone, A., Palamara, A. T. (2008). Increase of Virulence and Its Phenotypic Traits in Drug-Resistant Strains of Candida albicans. Antimicrob. Agents Chemother. 52: 927-936 [Abstract] [Full Text]  
• Uppuluri, P., Nett, J., Heitman, J., Andes, D. (2008). Synergistic Effect of Calcineurin Inhibitors and Fluconazole against Candida albicans Biofilms. Antimicrob. Agents Chemother. 52: 1127-1132 [Abstract] [Full Text]  
• Hiller, E., Heine, S., Brunner, H., Rupp, S. (2007). Candida albicans Sun41p, a Putative Glycosidase, Is Involved in Morphogenesis, Cell Wall Biogenesis, and Biofilm Formation. Eukaryot Cell 6: 2056-2065 [Abstract] [Full Text]