JAC Advance Access published online on December 20, 2008
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkn515
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Original research |
Effect of tunicamycin on Candida albicans biofilm formation and maintenance
Department of Biology and South Texas Center for Emerging Infectious Diseases, The University of Texas at San Antonio, San Antonio, TX, USA
Received 8 September 2008; returned 21 October 2008; revised 21 November 2008; accepted 25 November 2008
* Corresponding author. Tel: +1-210-458-7022; Fax: +1-210-458-7023; E-mail: jose.lopezribot{at}utsa.edu
Background: Candida albicans is a common opportunistic pathogen of the human body and is the frequent causative agent of candidiasis. Typically, these infections are associated with the formation of biofilms on both host tissues and implanted biomaterials. As a result of the intrinsic resistance of C. albicans biofilms to most antifungal agents, new strategies are needed to combat these infections.
Methods: Here we have used a 96-well microtitre plate model of C. albicans biofilm formation to study the inhibitory effect of tunicamycin, a nucleoside antibiotic that inhibits N-linked glycosylation affecting cell wall and secreted proteins, on C. albicans biofilm formation. A proteomic approach was used to study the effect of tunicamycin on levels of glycosylation of key secreted mannoproteins in the biofilm matrix.
Results: Our results revealed that physiological concentrations of tunicamycin displayed significant inhibitory effects on biofilm development and maintenance, while not affecting overall cell growth or morphology. However, tunicamycin exerted a minimal effect on fully mature, pre-formed C. albicans biofilms.
Conclusions: The effect of tunicamycin on the C. albicans biofilm mode of growth demonstrates the importance of N-linked glycosylation in the developmental stages of biofilm formation. In addition, our results indicate that N-linked glycosylation represents an attractive target for the development of alternative strategies for the prevention of biofilm formation by this important pathogenic fungus.
Key Words: microbial communities , N-glycosylation , cell wall mannoproteins , candidiasis