Ubiquitously expressed Human Beta Defensin 1 (hBD1) forms bacteria-entrapping nets in a redox dependent mode of action

PLoS Pathogens

Heike Brötz-Oesterhelt¹  Anne Berscheid¹  Adam A. Strömstedt²  Judith Raschig³  Nisar P. Malek³  Jan Wehkamp³  Daniela Mailänder-Sánchez³  Lioba F. Courth³  Jürgen Berger⁴ 

[1] Department for Microbial Bioactive Compounds, Interfaculty Institute for Microbiology and Infection Medicine, University of Tuebingen, Tuebingen, Germany;Division of Pharmacognosy, Department of Medicinal Chemistry, Uppsala University, Biomedical Centre, Uppsala, Sweden;Internal Medicine I, University Hospital Tuebingen, Tuebingen, Germany;Max-Planck Institute for Developmental Biology, Electron Microscopy, Tuebingen, Germany

关键词: Bacteria;    Cell membranes;    Antimicrobials;    Scanning electron microscopy;    Cysteine;    Klebsiella pneumoniae;    Liposomes;    Defensins;   

DOI  :  10.1371/journal.ppat.1006261

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Ever since the discovery of endogenous host defense antimicrobial peptides it has been discussed how these evolutionary conserved molecules avoid to induce resistance and to remain effective. Human ß-defensin 1 (hBD1) is an ubiquitously expressed endogenous antimicrobial peptide that exhibits qualitatively distinct activities between its oxidized and reduced forms. Here, we explore these antimicrobial mechanisms. Surprisingly, using electron microscopy we detected a so far unknown net-like structure surrounding bacteria, which were treated with the reduced but not the oxidized form of hBD1. A transmigration assay demonstrated that hBD1-derived nets capture bacteria and inhibit bacterial transmigration independent of bacterial killing. The presence of nets could completely prevent migration of hBD1 resistant pathogens and are stable in the presence of human duodenal secretion with a high amount of proteases. In contrast to HD6, cysteins are necessary for net formation. This redox-dependent function serves as an additional mechanism of action for hBD1 and differs from net formation by other defensins such as Paneth cell-derived human α-defensin 6 (HD6). While hBD1red and hBD1ox have distinct antimicrobial profiles and functions, only the reduced form provides additional host protection by entrapping bacteria in extracellular net structures preventing bacterial invasion. Better understanding of the modes of action of endogenous host peptides will help to find new antimicrobial strategies.

【 授权许可】

CC BY