Antibacterial Effects of Lactoferrin and a Pepsin-Generated Lactoferrin Peptide Against Helicobacter pylori in vitro

Helicobacter pylori is an etiologic agent of gastritis and peptic ulcer disease in humans. We investigated the antibacterial activities of lactoferrin and Lactoferricin® (an antimicrobial peptide derived from lactoferrin) against this bacterium. The minimum bactericidal concentrations of bovine and human lactoferrins were 1.25 to 2.50 mg/mL, while it was greater than 5.0 mg/L for bovine Lactoferricin®. Time-kill studies withH. pylori grown in brucella broth demonstrated that the antibacterial effects of the lactoferrins were dose-dependent within the range of 0.8 to 2.0 mg/mL and began when the cells were in the exponential phase of growth. Iron-saturated lactoferrin did not inhibit the growth ofH. pylori. Bovine Lactoferricin® showed only weak activity againstH. pylori in brucella broth, however, a rapid bactericidal effect was observed in 1% Bacto-peptone medium within 1 hour of exposure at concentrations in the range of 0.1 to 1.0 mg/mL. Under these conditions, bovine lactoferrin showed little effect. Moreover, bovine Lactoferricin® inhibited the urease activity ofH. pylori, which is one of the virulence factors of this bacterium. These results indicate thatH. pylori is susceptible to inhibition and inactivation by both lactoferrin and Lactoferricin® in laboratory media. The antibacterial effect of lactoferrin appeared to be dependent on its iron status, the cellular phase of growth, and has a mechanism of action different from that of Lactoferricin®.