ABSTRACT
Staphylococcus aureus community-acquired (CA) MRSA strains are highly virulent and can cause infections in otherwise healthy individuals. The most important mechanism of the host for clearing S. aureus is phagocytosis by neutrophils and subsequent killing of the pathogen. Especially CA-MRSA strains are very efficient in circumventing this neutrophil killing. Interestingly, only a relative small number of virulence factors have been associated with CA-MRSA, one of which are the phenol soluble modulins (PSMs). We have recently shown that the PSMs are functionally inhibited by serum lipoproteins, indicating that PSMs may exert their cytolytic function primarily in the intracellular environment. To further investigate the intracellular role of the PSMs we measured the effect of the α-type and ß-type PSMs on neutrophil killing after phagocytosis. Using fluorescently labelled S. aureus, we measured bacterial survival after phagocytosis in a plate reader, which was employed next to flow cytometry and time-lapse microscopy. Phagocytosis of the CA-MRSA strain MW2 by human neutrophils resulted in rapid host cell death. Using mutant strains of MW2, we demonstrated that in the presence of serum, the intracellular expression of only the psmα operon is both necessary and sufficient for both increased neutrophil cell death and increased survival of S. aureus. Our results identify PSMα peptides as prominent contributors to killing of neutrophils after phagocytosis, a finding with major implications for our understanding of S. aureus pathogenesis and strategies for S. aureus vaccine development.
Subject(s)
Bacterial Toxins/metabolism , Methicillin-Resistant Staphylococcus aureus/metabolism , Neutrophils/pathology , Phagocytosis/physiology , Antibodies, Anti-Idiotypic/immunology , Bacterial Toxins/antagonists & inhibitors , Bacterial Toxins/immunology , Bacterial Vaccines/immunology , Bacterial Vaccines/therapeutic use , Cell Death/physiology , Cells, Cultured , Humans , Neutrophils/physiologyABSTRACT
Insurance medicine is becoming more and more important. Currently, there are few countries in Europe where insurance medicine is recognised as an independent discipline; the Netherlands is one example. Since 2007 the "Specialist in Insurance Medicine and Medico-legal Expertise" is recognised in Belgium. This article will give an overview of the residency of Flemish physicians. By enactment, this consists of a theoretical and a practical section. This way of education should open broad possibilities in private and social insurance medicine, but also in the research sector.
