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Bas Surewaard

Monday 22 April 2013

Immune evasion by Gram-positive pathogens

Promotor: Prof.dr Jos van Strijp
Defence: 22 April 2013

In this thesis immune evasion mechanisms of Gram-positive pathogens were investigated. Staphylococcus aureus is becoming a bigger problem every day especially with rise of antibiotic resistance. Community-associated methicillin- resistant S. aureus (CA-MRSA) is able to cause infections in otherwise healthy individuals. Phenol soluble modulins (PSMs) are one of the few virulence factors associated with these CA-MRSA strains. In this thesis found that PSMs are inactivated by serum lipoproteins and that they function different than hypothesized. PSMs are up-regulated upon phagocytosis and can lyse neutrophils from within. These findings have major implications for our understanding of S. aureus pathogenesis and strategies for S. aureus vaccine development. Furthermore we identified a new virulence factor for another major human pathogens Streptococcus pneumoniae. Zinc metalloprotease C efficiently cleaves PSGL-1 form human neutrophils and thereby hampers the recruitment of neutrophils to the site of infection.