Amyloidogenic amyloid-β-peptide variants induce microbial agglutination and exert antimicrobial activity.
Amyloid-β (Aβ) peptides are the main components of the plaques found in the brains of patients with Alzheimer's disease. However, Aβ peptides are also detectable in secretory compartments and peripheral blood contains a complex mixture of more than 40 different modified and/or N- and C-terminally truncated Aβ peptides. Recently, anti-infective properties of Aβ peptides have been reported. Here, we investigated the interaction of Aβ peptides of different lengths with various bacterial strains and the yeast Candida albicans. The amyloidogenic peptides Aβ1-42, Aβ2-42, and Aβ3p-42 but not the non-amyloidogenic peptides Aβ1-40 and Aβ2-40 bound to microbial surfaces. As observed by immunocytochemistry, scanning electron microscopy and Gram staining, treatment of several bacterial strains and Candida albicans with Aβ peptide variants ending at position 42 (Aβx-42) caused the formation of large agglutinates. These aggregates were not detected after incubation with Aβx-40. Furthermore, Aβx-42 exerted an antimicrobial activity on all tested pathogens, killing up to 80% of microorganisms within 6 h. Aβ1-40 only had a moderate antimicrobial activity against C. albicans. Agglutination of Aβ1-42 was accelerated in the presence of microorganisms. These data demonstrate that the amyloidogenic Aβx-42 variants have antimicrobial activity and may therefore act as antimicrobial peptides in the immune system.
Department of Psychiatry and Psychotherapy, Friedrich-Alexander-University Erlangen-Nuremberg, Schwabachanlage 6, D-91054 Erlangen, Germany.
Philipp
P
Spitzer
Department of Psychiatry and Psychotherapy, Friedrich-Alexander-University Erlangen-Nuremberg, Schwabachanlage 6, D-91054 Erlangen, Germany.
Mateja
M
Condic
Department of Medicine III, Institute for Clinical Immunology, Friedrich-Alexander-University Erlangen-Nuremberg, Gluecksstraße 4a, D-91054 Erlangen, Germany.
Martin
M
Herrmann
Department of Psychiatry and Psychotherapy, Friedrich-Alexander-University Erlangen-Nuremberg, Schwabachanlage 6, D-91054 Erlangen, Germany.
Timo Jan
TJ
Oberstein
Electron Devices, Friedrich-Alexander-University Erlangen-Nuremberg, Cauerstraße 6, D-91058 Erlangen, Germany.
Marina
M
Scharin-Mehlmann
Institute of Medical Biotechnology, Friedrich-Alexander-University Erlangen-Nuremberg, Paul-Gordan-Str. 3, D-91052 Erlangen, Germany.
Daniel F
DF
Gilbert
Institute of Medical Biotechnology, Friedrich-Alexander-University Erlangen-Nuremberg, Paul-Gordan-Str. 3, D-91052 Erlangen, Germany.
Oliver
O
Friedrich
Department of Psychiatry and Psychotherapy, Friedrich-Alexander-University Erlangen-Nuremberg, Schwabachanlage 6, D-91054 Erlangen, Germany.
Teja
T
Grömer
Department of Psychiatry and Psychotherapy, Friedrich-Alexander-University Erlangen-Nuremberg, Schwabachanlage 6, D-91054 Erlangen, Germany.
Johannes
J
Kornhuber
Institute of Clinical Microbiology, Immunology and Hygiene, Friedrich-Alexander-University Erlangen-Nuremberg, Wasserturmstr. 3/5, D-91054 Erlangen, Germany.
Roland
R
Lang
Department of Psychiatry and Psychotherapy, Friedrich-Alexander-University Erlangen-Nuremberg, Schwabachanlage 6, D-91054 Erlangen, Germany.
Juan Manuel
JM
Maler
D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000494:pharmacology*; D000890:Anti-Infective Agents / Q000494:pharmacology*; D001419:Bacteria / Q000145:classification / Q000187:drug effects*; D002176:Candida albicans / Q000187:drug effects*; D013293:Enterococcus faecalis / Q000187:drug effects / Q000648:ultrastructure; D006801:Humans; D050296:Microbial Viability / Q000187:drug effects; D008855:Microscopy, Electron, Scanning; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology*
D016229:Amyloid beta-Peptides; D000890:Anti-Infective Agents; D010446:Peptide Fragments