Abstract

Antibacterial peptides are part of the innate immune system in a variety of different species including humans. Some of these peptides have also been shown to have effects on immune competent cells such as professional phagocytes. We have recently shown that a cecropin-like peptide from Helicobacter pylori, Hp(2-20), in addition to being bactericidal possesses proinflammatory effects and can recruit and activate neutrophils as well as monocytes. It is well established that cecropins have the ability to adopt amphipathic alpha-helices, which is thought to be required for their bactericidal activity. In this study we show the same structural requirements for Hp(2-20). Breaking the helical structure of Hp(2-20) reduced the antibacterial effect and abolished its proinflammatory activity. A C-terminal truncated cecropin A peptide that highly resembles Hp(2-20) failed to activate neutrophils and computer-based structural simulations revealed a difference between the two peptides in the stability of their helical structures. A hybrid peptide with amino acid substitutions stabilizing the alpha-helical structure of the truncated cecropin A peptide did not introduce any proinflammatory activity; the bactericidal activity was, however, increased. We thus conclude that the proinflammatory effect of Hp(2-20) is a unique sequence-specific feature of the peptide and the ability to adopt a stable amphipathic helix is a necessary but not sufficient criterion for the functional dualism of the peptide.