Structure-Function Characterization and Optimization of a Plant-Derived Antibacterial Peptide

Titelangaben

Suarez, Mougli ; Haenni, Marisa ; Canarelli, Stéphane ; Fisch, Florian ; Chodanowski, Pierre ; Servis, Catherine ; Michielin, Olivier ; Freitag, Ruth ; Moreillon, Philippe ; Mermod, Nicolas:
Structure-Function Characterization and Optimization of a Plant-Derived Antibacterial Peptide.
In: Antimicrobial Agents and Chemotherapy. Bd. 49 (2005) Heft 9 . - S. 3847-3857.
ISSN 1098-6596
DOI: https://doi.org/10.1128/AAC.49.9.3847-3857.2005

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Abstract

Crushed seeds of the Moringa oleifera tree have been used traditionally as natural flocculants to clarify drinking water. We previously showed that one of the seed peptides mediates both the sedimentation of suspended particles such as bacterial cells and a direct bactericidal activity, raising the possibility that the two activities might be related. In this study, the conformational modeling of the peptide was coupled to a functional analysis of synthetic derivatives. This indicated that partly overlapping structural determinants mediate the sedimentation and antibacterial activities. Sedimentation requires a positively charged, glutamine-rich portion of the peptide that aggregates bacterial cells. The bactericidal activity was localized to a sequence prone to form a helix-loop-helix structural motif. Amino acid substitution showed that the bactericidal activity requires hydrophobic proline residues within the protruding loop. Vital dye staining indicated that treatment with peptides containing this motif results in bacterial membrane damage. Assembly of multiple copies of this structural motif into a branched peptide enhanced antibacterial activity, since low concentrations effectively kill bacteria such as Pseudomonas aeruginosa and Streptococcus pyogenes without displaying a toxic effect on human red blood cells. This study thus identifies a synthetic peptide with potent antibacterial activity against specific human pathogens. It also suggests partly distinct molecular mechanisms for each activity. Sedimentation may result from coupled flocculation and coagulation effects, while the bactericidal activity would require bacterial membrane destabilization by a hydrophobic loop.