Effect of tunicamycin on Candida albicans biofilm formation and maintenance.
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.
Pierce
Christopher G
CG
Department of Biology and South Texas Center for Emerging Infectious Diseases, The University of Texas at San Antonio, San Antonio, TX, USA.
Thomas
Derek P
DP
López-Ribot
José L
JL
D018441:Biofilms / Q000187:drug effects* / Q000254:growth & development*; D002176:Candida albicans / Q000737:chemistry / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005656:Fungal Proteins / Q000378:metabolism; D006031:Glycosylation / Q000187:drug effects; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism; D020543:Proteome / Q000032:analysis; D014415:Tunicamycin / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D005656:Fungal Proteins; D008562:Membrane Glycoproteins; D020543:Proteome; C025363:mannoproteins; D014415:Tunicamycin