A bactericidal cecropin-A peptide with a stabilized alpha-helical structure possess an increased killing capacity but no proinflammatory activity

• 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Mikrobiologi inom det medicinska området (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Microbiology in the medical area (hsv//eng)

Nyckelord

Amino Acid Sequence

*Anti-Bacterial Agents/chemistry/pharmacology

purification/*pharmacology

Computer Simulation

Escherichia coli/drug effects/genetics

Helicobacter pylori/chemistry

Humans

*Inflammation

Microbial Sensitivity Tests

Models

Molecular

NADPH Oxidase/analysis/metabolism

Neutrophils/drug effects/enzymology

Peptides/*chemistry/isolation & purification/*pharmacology

Protein Structure

Secondary

Superoxides/analysis

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