Staphylococcus aureus cardiolipin production and role in host-pathogen interactions

Projektinformationen

S. AUREUS CLS

ID Finanzhilfevereinbarung: 249285

Abgeschlossenes Projekt

Startdatum 3 Mai 2010

Enddatum 2 Mai 2014

Finanziert unter

• Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)

Gesamtkosten € 100 000,00

EU-Beitrag € 100 000,00

Koordiniert durch

KEMIJSKI INSTITUT
Slovenia

Ziel

Staphylococcus aureus infections are associated with significant morbidity and mortality in healthcare and community settings. Inside the host, invading S. aureus is challenged by host innate immune defenses that include professional phagocytes and an arsenal of secreted antimicrobials. Long term persistence of S. aureus may be due to adoption of quiescent physical and metabolic states, such as biofilms, endocardial vegetations, and small colony variants. The metabolic changes needed for adaptation and long term survival inside the host are largely unknown. Our preliminary studies have revealed a pronounced metabolic switch that results in a change of the membrane composition from the major phospholipid phosphatidylglycerol (PG) to cardiolipin (CL). This striking lipid change occurs when S. aureus is phagocytosed by neutrophils and can also be mimicked in vitro in the stationary phase of growth, or through ATP depletion. Our central hypothesis is that adaptive lipid changes are essential for optimal survival of S. aureus under adverse conditions. In bacteria, CL is mainly synthesized by membrane-bound cardiolipin synthase enzymes (CLS). The S. aureus genome contains two open reading frames putatively encoding CLS, each with ~30% identity to the E. coli CLS enzymes. The function of the two S. aureus CLSs have not been explored and will be the focus of this grant proposal. Towards this end, we will investigate the: (i) function of CLS enzyme 1 and enzyme 2 in lipid metabolism, (II) role of CL in lipoteichoic acid generation, (III) requirement for CL during in vitro persistence and survival in planktonic cultures, in (IV) endocardial vegetations, and (V) interactions with host defenses. Understanding of the molecular mechanisms and regulation of CL synthesis in S. aureus may uncover novel targets for the development of anti-Staphylococcal agents.

Wissenschaftliches Gebiet

• social sciences › sociology › demography › mortality
• natural sciences › biological sciences › microbiology › bacteriology
• natural sciences › biological sciences › biochemistry › biomolecules › lipids
• natural sciences › biological sciences › genetics › genomes
• natural sciences › biological sciences › biochemistry › biomolecules › proteins › enzymes

Programm/Programme

• FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)

Thema/Themen

• FP7-PEOPLE-2009-RG - Marie Curie Action: "Reintegration Grants"

Aufforderung zur Vorschlagseinreichung

FP7-PEOPLE-2009-RG
Andere Projekte für diesen Aufruf anzeigen

Finanzierungsplan

MC-IRG - International Re-integration Grants (IRG)

Koordinator

KEMIJSKI INSTITUT

Kontakt Verwaltung

Roman Jerala (Dr.)

• EU-Beitrag: € 100 000,00
• Adresse: HAJDRIHOVA 19 ; 1000 Ljubljana ; Slowenien
• Region: Slovenija › Zahodna Slovenija › Osrednjeslovenska
• Aktivitätstyp: Research Organisations
• Gesamtkosten: Keine Daten