Intravenous literature: Green, J.V., Orsborn, K.I., Zhang, M., Tan, Q.K., Greis, K.D., Porollo, A., Andes, D.R., Long, J.L. and Hostetter, M.K. (2013) Heparin Binding Motifs and Biofilm Formation by Candida albicans. The Journal of Infectious Diseases. July 31st. [Epub ahead of print].
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 ELISA assay. A sequence-based search identified 34 C. albicans surface proteins containing at least one match to linear heparin binding motifs (HBM). The virulence factor Int1 contained the largest number (five) of putative HBMs; peptides encompassing two of five motifs bound to heparin-Sepharose. Alanine substitution of lysine residues805/806 in 804QKKHQIHK (Motif 1 of Int1) markedly attenuated biofilm formation in central venous catheters in rats, whereas alanine substitution of lysine1595/arginine1596 in 1593FKKRFFKL (Motif 4 of Int1) did not impair biofilm formation. Affinity-purified IgG recognizing Motif 1 abolished biofilm formation in central venous catheters; pre-immune IgG had no effect. Soluble peptides from multiple C. albicans surface proteins such as Eno1, Pgk1, Tdh3, and Ssa1/2 but not Int1 were detected after heparin treatment of C. albicans, 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.