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Antioxidant deficiency linked to soil disease risk in diabetics

14 May 2012

Scanning electron micrograph of Burkholderia pseudomallei, the bacteria that cause melioidosis

Assoc Prof Gan (left) and Dr Tan Kai Soo, an assistant professor at the NUS Faculty of Dentistry who was a postdoctoral researcher and first author of the research paper

Melioidosis, a potentially deadly disease caused by the bacteria Burkholderia pseudomallei living in contaminated water or soil, has been observed to occur more frequently in diabetics. Little is known about the reason behind this until now, thanks to a discovery by Singapore scientists.

Researchers - comprising members from the NUS Departments of Biochemistry, Medicine and Microbiology, as well as the Defence Medical and Environmental Research Institute - have found that this increased risk in diabetics can be attributed to a deficiency in glutathione, a molecule with antioxidant property that protects the body from oxidative stress. The group has published the results in The Journal of Clinical Investigation.

Lead investigator Assoc Prof Gan Yunn Hwen from the Department of Biochemistry in the Yong Loo Lin School of Medicine explained that glutathione exists in two forms - a reduced version and an oxidised version. A deficiency in the reduced form impairs the white blood cells' capability in making immune factors known as IL-12 and Interferon-gamma, which are necessary to activate the blood cells to kill the bacteria within the cells.

This mechanism is likely not confined to melioidosis but may also be used to explain the susceptibility of diabetics to other bacterial diseases such as tuberculosis, she said.

Melioidosis is endemic in this region and up to 60 per cent of patients with the soil disease also have Type 2 diabetes, noted Assoc Prof Gan. The disease is very difficult to treat and requires prolonged antibiotic administration because the bacterium is highly resistant to antibiotics.

She said: "This will present a problem to resource-poor developing nations which have to deal with the disease. Furthermore, if we can find the link, then it is possible to reduce the diabetics' risk of getting severe melioidosis."

Singapore sees about 50 to 60 cases of melioidosis a year, usually in people with soil contact such as national servicemen, construction workers and soccer players, she said.

The team is awaiting approval from the Singapore Health Sciences Authority to start a clinical trial using the drug Fluimucil (N-acetylcysteine) which shows promise in increasing the ability of immune cells from diabetics to kill the melioidosis bacterium. Prof Lee Kok Onn from the Department of Medicine is leading the trial.

The study, which started in 2007, has received grants of about S$268,000 from the National Medical Research Council and S$50,000 from the Mindef-NUS Joint Applied R&D Co-operation Programme.