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  • Heparin-Binding Motifs and Biofilm Formation by Candida albicans

    Bc387102g?file=thumbnail
    Type:
    Article
    Description/Abstract:
    Candida albicans is a leading pathogen in infections of central venous catheters, which are frequently infused with heparin. Binding of C. albicans to medically relevant concentrations of soluble and plate-bound heparin was demonstrable by confocal microscopy and enzyme-linked immunosorbent assay (ELISA). A sequencebased search identified 34 C. albicans surface proteins containing ≥1 match to linear heparin-binding motifs. The virulence factor Int1 contained the most putative heparin-binding motifs (n = 5); peptides encompassing 2 of 5 motifs bound to heparin-Sepharose. Alanine substitution of lysine residues K805/K806 in 804QKKHQIHK811 (motif 1 of Int1) markedly attenuated biofilm formation in central venous catheters in rats, whereas alanine substitution of K1595/R1596 in 1593FKKRFFKL1600 (motif 4 of Int1) did not impair biofilm formation. Affinity-purified immunoglobulin G (IgG) recognizing motif 1 abolished biofilm formation in central venous catheters; preimmune IgG had no effect. After heparin treatment of C. albicans, soluble peptides from multiple C. albicans surface proteins were detected, such as Eno1, Pgk1, Tdh3, and Ssa1/2 but not Int1, suggesting that heparin changes candidal surface structures and may modify some antigens critical for immune recognition. These studies define a new mechanism of biofilm formation for C. albicans and a novel strategy for inhibiting catheter-associated biofilms.
    Creator/Author:
    Orsborn, Kris I.; Lu, Jason Long; Green, Julianne V.; Porollo, Alexey; Hostetter, Margaret K.; Tan, Queenie K., G.; Zhang, Minlu; Andes, David R., and Greis, Kenneth D.
    Submitter:
    Kenneth Greis
    Date Uploaded:
    03/03/2017
    Date Modified:
    04/07/2017
    Date Created:
    2013-07
    License:
    All rights reserved