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Lowering cholesterol good for us, bad for bacteria

Sun, 17th Feb 2008

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Scientists in the US have discovered a novel way to tackle problem superbugs like MRSA - by disabling their defences with a cholesterol-lowering drug.

CarrotsUCSD researcher Victor Nizet and his team initially noticed that bugs like Staph aureus (MRSA) produce a yellow-coloured family of antioxidants called carotenoids (also found in carrots), which protect them against free-radicals and other oxidising agents produced by the immune system to destroy bacterial cells.  When the researchers knocked out the gene used by the bacteria to produce these chemicals the bugs became much more vulnerable to immune attack.

Looking for ways to neutralise the gene in bacteria that cause infections in patients, co-author Eric Oldfield realised that the building blocks used by the bacteria to make their carotenoid antioxidants were almost identical to the chemicals used in humans to produce cholesterol.  In particular one gene, called squalene synthase was strikingly similar.  Acting on this insight the researchers began to screen compounds developed previously as cholesterol lowering drugs that target this pathway.  One agent, called BPH-652, was very effective at penetrating Staphylococcal cells and blocking their ability to produce carotenoids.

"We have found that the same golden armour used by Staph to thwart our immune system can also be its achilles heel" says Nivet. And because BPH-652 has previously been tested in human clinical trials it should be the costs and time required for it to enter the clinical should be lower.

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