PSMS-IN-INFLAMMATION

Imaging Innate Immunity of Staphylococcal Infections

Coordinatore	more  Organization address address: HEIDELBERGLAAN 100 city: UTRECHT postcode: 3584 CX contact info Nome: Susan Cognome: Zwaagstra Email: send email Telefono: +31 88 7553017 Fax: +31 887555863
Nazionalità Coordinatore	Non specificata
Totale costo	259˙582 €
EC contributo	259˙582 €
Programma	FP7-PEOPLE Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)
Code Call	FP
Anno di inizio	2014
Periodo (anno-mese-giorno)	2014-04-09   -   2017-04-08

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	UNIVERSITAIR MEDISCH CENTRUM UTRECHT  Organization address address: HEIDELBERGLAAN 100 city: UTRECHT postcode: 3584 CX contact info Nome: Susan Cognome: Zwaagstra Email: send email Telefono: +31 88 7553017 Fax: +31 887555863	NL (UTRECHT)	coordinator	259˙582.50

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 Obiettivo del progetto (Objective)

'Staphylococcus aureus community-acquired (CA)-MRSA strains are highly virulent and can cause infections in otherwise healthy individuals and are a leading cause of death worldwide. Innate immunity is our primary defense against invading staphylococci. Blood-neutrophils migrate to the site of infection where they, in concert with the complement system, engulf and kill bacteria in a process called phagocytosis. Especially CA-MRSA strains seem to be 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). In vivo models of experimental infection with PSM-mutants have shown a critical role for PSMs in skin and soft tissue infections. PSMs are small alpha-helical peptides which have two distinct functions on the immune system, in vitro PSMs can attract neutrophils in the nanomolar range, whereas in the micromolar range they are cytolytic for neutrophils. Recent publications suggests that these two functions complement each other for full staphylococcal virulence, although it seems counter-intuitive for S. aureus to actively attract its mortal enemy: the neutrophil. To make matters even more complicated PSMs are functionally inactivated by host serum lipoproteins, most efficiently by high density lipoprotein (HDL). The goal of this research proposal is to determine the mechanism of action for PSMs in staphylococcal disease. To this end, I will use genomic and proteomic approaches combined with cutting edge in vivo spinning-disk confocal microscopy, to dissect the functions of PSMs in host-staphylococcal interactions in; 1) neutrophil recruitment, 2) neutrophil lysis 3) HDL neutralization and liver pathology, 4) Evasion of PSM-recognition by FLIPR-L'