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Staphylococcus aureus cardiolipin production and role in host-pathogen interactions

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Breaching bacterial defences

Overcoming the ingenious defence systems of Staphylococcus aureus (S. aureus) will cause a sigh of relief in healthcare circles. A European project has made headway into identifying the molecular basis behind protective changes in the bacterium's membrane.

Health

S. aureus is the bane of hospital and community healthcare settings. Despite bombardment by the host's immune complement including professional phagocytes and many secreted antimicrobials, S. aureus can persist long term using a battery of physical and metabolic states. One such metabolic survival system is to change the membrane composition from the phospholipid, phosphatidylglycerol (PG) to cardiolipin (CL). This spectacular change occurs when the bacterium is challenged with a type of professional phagocyte, the neutrophil. The 'Staphylococcus aureus cardiolipin production and role in host-pathogen interactions' (S. Aureus CLS) project aimed to investigate this lipid change phenomenon. Project scientists postulated that this mechanism was central to the survival of the pathogen in adverse conditions. CL is synthesised using cardiolipin synthase (Cls) enzymes at the membrane. As very little is known about these enzymes, the S. Aureus CLS team aimed to investigate their role in lipid metabolism and in the synthesis of membrane lipoteichoic acid. Regarding defences against the host immune system, the scientists also investigated the role of CL in persistent infections and interactions with host defences as well as endocardial vegetations. S. aureus is one of the few bacteria able to colonise the heart endothelium. By expressing the open reading frames (ORFs) of two Cls genes in Escherichia coli (E. coli) and creating single and double mutants for the two genes, the scientists determined the roles of Cls1 and Cls2. Differences in contribution of the two enzymes suggest that they play different roles under a variety of different triggering conditions. For example, CL accumulation in the stationary phase was due almost entirely to Cls2 expression. However, both Cls1 and Cls2 were required for CL production during neutrophil attack. Continuing project research will focus on the biological role of CL in S. aureus survival. Its function when faced with one of the antimicrobial phospholipases will be examined as well as survival in more complex environments like the endocardium. A molecular picture of the strategies evolved in S. aureus to bypass the host's innate immune onslaught will undoubtedly help to reduce the fatalities caused by complications and infections by this bacterium. The urgency of this issue in healthcare is compounded by the existence of strains resistant to many anti-microbials.

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