Microbicidal action of lactoferrin and lactoferricin and their synergistic effect with metronidazole in Entamoeba histolytica.

Lactoferrin (Lf), in its iron-free form, has been shown to inhibit the growth of pathogenic microorganisms. In the light of new agents to control amoebiasis, the microbicidal activity of human and bovine Lf and bovine lactoferricin (bLfcin, fragment 4-14), and of each combined with metronidazole, the main drug used in amoebiasis, was evaluated in trophozoites of Entamoeba histolytica. Both lactoferrins and bLfcin were able to kill amoebas in a concentration-dependent manner. This killing effect was modulated according to the culture age, pH, and temperature. Parasites obtained from the stationary phase were more susceptible to Lf than those from the early exponential phase. The effect of Lf and its derived peptide, bLfcin, was prevented by both Fe2+ and Fe3+. However, the divalent cations Mg2+ and Ca2+ prevented the killing effect of Lf but not of bLfcin. A synergistic amoebicidal effect was found between metronidazole and human Lf, bovine Lf, or bLfcin. These data suggest that Lf and bLfcin might be used in amoebiasis if they are administered with a low dose of metronidazole to diminish the toxicity of this drug. Thus, Lf and bLfcin are therapeutically potential candidates for use as antiamoebics in patients.