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

Abstract

<i>Helicobacter pylori</i> 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 2.50mg/mL, while it was greater than 5.0mg/L for bovine Lactoferricin^®. Time-kill studies with <i>H. pylori</i> grown in brucella broth demonstrated that the antibacterial effects of the lactoferrins were dose-dependent within the range of 0.8 to 2.0mg/mL and began when the cells were in the exponential phase of growth. Iron-saturated lactoferrin did not inhibit the growth of <i>H. pylori</i>. Bovine Lactoferricin^® showed only weak activity against <i>H. pylori</i> 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 1.0mg/mL. Under these conditions, bovine lactoferrin showed little effect. Moreover, bovine Lactoferricin^® inhibited the urease activity of <i>H. pylori</i>, which is one of the virulence factors of this bacterium. These results indicate that <i>H. pylori</i> 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^®.