Cel
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.
Dziedzina nauki
Klasyfikacja projektów w serwisie CORDIS opiera się na wielojęzycznej taksonomii EuroSciVoc, obejmującej wszystkie dziedziny nauki, w oparciu o półautomatyczny proces bazujący na technikach przetwarzania języka naturalnego.
Klasyfikacja projektów w serwisie CORDIS opiera się na wielojęzycznej taksonomii EuroSciVoc, obejmującej wszystkie dziedziny nauki, w oparciu o półautomatyczny proces bazujący na technikach przetwarzania języka naturalnego.
Zaproszenie do składania wniosków
FP7-PEOPLE-2009-RG
Zobacz inne projekty w ramach tego zaproszenia
System finansowania
MC-IRG - International Re-integration Grants (IRG)Koordynator
1000 Ljubljana
Słowenia