Ubiquitously expressed Human Beta Defensin 1 (hBD1) forms bacteria-entrapping nets in a redox dependent mode of action.
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.
Internal Medicine I, University Hospital Tuebingen, Tuebingen, Germany.
Judith
J
Raschig
Internal Medicine I, University Hospital Tuebingen, Tuebingen, Germany.
Daniela
D
Mailänder-Sánchez
Department for Microbial Bioactive Compounds, Interfaculty Institute for Microbiology and Infection Medicine, University of Tuebingen, Tuebingen, Germany.
Anne
A
Berscheid
Max-Planck Institute for Developmental Biology, Electron Microscopy, Tuebingen, Germany.
Jürgen
J
Berger
Division of Pharmacognosy, Department of Medicinal Chemistry, Uppsala University, Biomedical Centre, Uppsala, Sweden.
Adam A
0000-0001-9070-6944
AA
Strömstedt
Internal Medicine I, University Hospital Tuebingen, Tuebingen, Germany.
Lioba F
0000-0003-4665-4096
LF
Courth
Internal Medicine I, University Hospital Tuebingen, Tuebingen, Germany.
Nisar P
NP
Malek
Department for Microbial Bioactive Compounds, Interfaculty Institute for Microbiology and Infection Medicine, University of Tuebingen, Tuebingen, Germany.
Heike
H
Brötz-Oesterhelt
Internal Medicine I, University Hospital Tuebingen, Tuebingen, Germany.
Jan
0000-0002-2311-5826
J
Wehkamp
D001419:Bacteria / Q000276:immunology*; D001826:Body Fluids / Q000378:metabolism; D004386:Duodenum / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D008854:Microscopy, Electron; D010084:Oxidation-Reduction; D023083:beta-Defensins / Q000276:immunology* / Q000378:metabolism
C406407:DEFB1 protein, human; D023083:beta-Defensins