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Candida albicans was found to be highly susceptible to inhibition and inactivation by lactoferricin B, a peptide produced by enzymatic cleavage of bovine lactoferrin. Effective concentrations of the peptide varied within the range of 18 to 150 g/ml depending on the strain and the culture medium used. Its effect was lethal, causing a rapid loss of colony-forming capability. 14C-labeled lactoferricin B bound to C. albicans and the rate of binding appeared to be consistent with the rate of killing induced by the peptide. The extent of binding was diminished in the presence of Mg2+ or Ca2+ ions which acted to reduce its anticandidal effectiveness. Binding occurred optimally at pH 6.0 and killing was maximal near the same pH. Such evidence suggests the lethal effect of lactoferricin B results from its direct interaction with the cell surface. Cells exposed to lactoferricin B exhibited profound ultrastructural damage which appeared to reflect its induction of an autolytic response. These findings suggest that active peptides of lactoferrin could potentially contribute to the host defense against C. albicans.

The effects of lactoferrin (LF), an antimicrobial protein secreted in body fluids, and its peptides in combination with azole antifungal agents were investigated by the micro-broth-dilution method in a study of Candida albicans. In the case of LF, its pepsin hydrolysate (LFhyd) or the LF-derived antimicrobial peptide Lactoferricin B (LF-B), the concentrations required to inhibit the growth of Candida decreased in the presence of relatively low concentrations of clotrimazole (CTZ). The minimum inhibitory concentration (MIC) of all azole antifungal agents tested was reduced by 1/4-1/16 in the presence of a sub-MIC level of each of these LF-related substances. Polyene and fluoropyrimidine antifungal agents did not show such a combined effect with these LF-related substances. The anti-Candida activity of LF or LF-B in combination with CTZ was shown to be synergistic by checkerboard analysis. These results indicate that LF-related substances function cooperatively with azole antifungal agents against C. albicans.



Since iron-binding proteins in serum and external secretions inhibit growth of certain microorganisms, the effect of lactoferrin on growth of Candida albicans was determined. The iron-unsaturated protein markedly impaired replication of the yeast, and the growth-inhibitory property was lost when lactoferrin was saturated with iron.