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Researchers in South East Asia have identified a novel mechanismwhereby the organism Burkholderia pseudomallei - the cause of melioidosis, a neglected tropical infectiousdisease - develops resistance to ceftazidime, the standard antibiotic treatment. The change also makes the drug-resistant bacteriumdifficult to detect. B. pseudomallei is found in water and soil predominately in tropical climates andespecially in South East Asia. It can infect both humans andanimals and causes melioidosis. The disease often occurs in peoplewho have underlying diseases such as type 2 diabetes or renal disease. Symptoms range from relatively mild to severe,and the mortality rate in Asia is as high as four out of ten cases. Infection is treated using ceftazidime, a third-generationcephalosporin -lactam antibiotic, which is a derivative ofpenicillin. This drug is often required for several weeks, duringwhich the bacteria may develop resistance to it. Now, in a paperpublished in the Proceedings of the National Academy of Science, researchers from the Wellcome Trust-Mahidol University-OxfordTropical Medicine Research Programme in Bangkok, Thailand, and theUniversity of Cambridge, in collaboration with Colorado StateUniversity and Genome Institute of Singapore, have identified howthe bacteria develop this resistance. By comparing the genetic make-up of isolates taken from sixpatients that had become resistant to ceftazidime against theiroriginal infecting ceftazidime-susceptible strain, the researchersfound a common, large-scale genomic loss involving at least 49genes that is thought to arise spontaneously as the bacteriareplicate and mutate. The researchers were able to demonstrate thata specific gene within this region was the cause of the drugresistance. This gene provides the genetic 'code' to create aprotein that is important to bacterial cell division and that isnormally the target for ceftazidime. The researchers also found that these mutated forms of B. pseudomallei would not grow in common laboratory cultures, including bottlesthat are normally used to culture blood from people with bacterialinfections, as well as the routine culture media used in thediagnostic laboratory. This makes the detection of thedrug-resistant forms very difficult. Consequently, patientscarrying this strain could continue to be treated with drugs thathave become ineffective. Professor Sharon Peacock, the team lead and a professor of clinicalmicrobiology at both Mahidol University and the University ofCambridge, said: "Clinical treatment failure occurs in as many asone in six patients receiving ceftazidime for melioidosis. Themechanism described here represents the first explanation forfailure of ceftazidime therapy, may be a frequent but undetectedevent, and provides us with an opportunity to seek ways to increasedetection of these variants." Dr Narisara Chantratita led the work undertaken at MahidolUniversity. She was awarded a Wellcome Trust IntermediateFellowship in Public Health and Tropical Medicine in 2009. Thisscheme provides support to researchers from low- and middle-incomecountries. Combating infectious diseases is one the strategic priorities ofthe Wellcome Trust. Much of this work is carried out at a locallevel in regions where disease is endemic. This includes severalmajor overseas programmes, including the Wellcome Trust-MahidolUniversity-Oxford Tropical Medicine Research Programme. Commenting on the research, Professor Danny Altmann, Head ofPathogens, Immunology and Population Health at the Wellcome Trust,said: "The development of drug resistance is a major concern fordoctors, particularly in low and middle income countries. Thisstudy helps us understand how resistance can occur and canhopefully lead to better detection and treatment of drug-resistantforms of melioidosis, a life-threatening tropical disease." Additional References Citations. The e-commerce company in China offers quality products such as Vibrating Sieve , Food Process Machinery Manufacturer, and more. For more , please visit Food Grinding Machine today!
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