Phenol-Soluble Modulin α Peptide Toxins from AggressiveStaphylococcus aureusInduce Rapid Formation of Neutrophil Extracellular Traps through a Reactive Oxygen Species-Independent Pathway.
Neutrophils have the ability to capture and kill microbes extracellularly through the formation of neutrophil extracellular traps (NETs). These are DNA and protein structures that neutrophils release extracellularly and are believed to function as a defense mechanism against microbes. The classic NET formation process, triggered by, e.g., bacteria, fungi, or by direct stimulation of protein kinase C through phorbol myristate acetate, is an active process that takes several hours and relies on the production of reactive oxygen species (ROS) that are further modified by myeloperoxidase (MPO). We show here that NET-like structures can also be formed by neutrophils after interaction with phenol-soluble modulin α (PSMα) that are cytotoxic membrane-disturbing peptides, secreted from community-acquired methicillin-resistantStaphylococcus aureus(CA-MRSA). The PSMα-induced NETs contained the typical protein markers and were able to capture microbes. The PSMα-induced NET structures were disintegrated upon prolonged exposure to DNase-positiveS. aureusbut not on exposure to DNase-negativeCandida albicans. Opposed to classic NETosis, PSMα-triggered NET formation occurred very rapidly, independently of ROS or MPO, and was also manifest at 4°C. These data indicate that rapid NETs release may result from cytotoxic membrane disturbance by PSMα peptides, a process that may be of importance for CA-MRSA virulence.
Department of Oral Microbiology and Immunology, Institute of Odontology, Sahlgrenska Academy at University of Gothenburg , Gothenburg , Sweden.
Halla
H
Björnsdottir
Department of Oral Microbiology and Immunology, Institute of Odontology, Sahlgrenska Academy at University of Gothenburg , Gothenburg , Sweden.
Agnes
A
Dahlstrand Rudin
Department of Oral Microbiology and Immunology, Institute of Odontology, Sahlgrenska Academy at University of Gothenburg , Gothenburg , Sweden.
Felix P
FP
Klose
The Phagocyte Research Laboratory, Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg , Gothenburg , Sweden.
Jonas
J
Elmwall
The Phagocyte Research Laboratory, Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg , Gothenburg , Sweden.
Amanda
A
Welin
Antifungal Immunity Group, Department of Clinical Microbiology, Umeå University , Umeå , Sweden.
Marios
M
Stylianou
Department of Oral Microbiology and Immunology, Institute of Odontology, Sahlgrenska Academy at University of Gothenburg , Gothenburg , Sweden.
Karin
K
Christenson
Antifungal Immunity Group, Department of Clinical Microbiology, Umeå University , Umeå , Sweden.
Constantin F
CF
Urban
The Phagocyte Research Laboratory, Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg , Gothenburg , Sweden.
Huamei
H
Forsman
The Phagocyte Research Laboratory, Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg , Gothenburg , Sweden.
Claes
C
Dahlgren
The Phagocyte Research Laboratory, Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg , Gothenburg , Sweden.
Anna
A
Karlsson
Department of Oral Microbiology and Immunology, Institute of Odontology, Sahlgrenska Academy at University of Gothenburg , Gothenburg , Sweden.
Johan
J
Bylund
FPR2; MPO; NETs; PSM; Papillon-Lefèvre syndrome; ROS; community-acquired methicillin-resistant Staphylococcus aureus; neutrophil elastase