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Antibiotic Resistance in Burkholderia pseudomallei



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21st February 2012

Burkholderia pseudomallei is a Gram-negative bacterium that causes the serious human disease, melioidosis. There is no vaccine against melioidosis and it can be fatal if not treated with a specific antibiotic regimen. B. pseudomallei is intrinsically resistant to many antibiotics, limiting the number of treatment options to a handful of drugs including the first line of defence, ceftazidime (CAZ) . CAZ has been highly successful for melioidosis treatment due in part to the low rate of primary resistance; however, resistance can develop through treatment especially in relapsing or recrudescent cases.
Our study identified and characterized two mutations leading to CAZ resistance. The first dramatically increased expression of a ?-lactamase which led to low-level resistance and cross-resistance to several other ?-lactam antibiotics some of which are used for melioidosis treatment. The second mutation led to very high-level CAZ resistance but sensitivity to several generic ?-lactams. In addition, using PCR we screened a very large collection (>2000) of environmental and clinical B. pseudomallei isolates for CAZ resistance. Our study showed that identification of resistance mechanisms and development of robust PCR assays will one day allow clinicians to monitor infections in real-time and alter treatment if a bacterial population develops resistance.

Prior to recently starting work at Menzies Dr Sarovich was a post-doctoral researcher at the Center for Microbial Genetics and Genomics in Flagstaff, Arizona. His primary research interests lie in antibiotic production, antibiotic resistance and in vivo evolution of pathogens..