GSK3 beta inhibition confers survival advantage in Burkholderia pseudomallei-infected hyperglycaemic mice by regulating inflammatory response

作者：Maniam P.; Kalimutho M.; Embi N.; Sidek H. M.^*

来源：Tropical Biomedicine, 2018, 35(1): 228-238.

Burkholderia pseudomallei, the etiologic agent of melioidosis is a common cause of sepsis mainly in diabetic individuals in South East Asia. Glycogen synthase kinase-3 beta (GSK3 beta) plays a pivotal role in modulating inflammatory balance in Gram-negative bacterial infections. In this study, we demonstrate that inhibition of GSK3 beta significantly improved survival of hyperglycaemic mice acutely infected with B. pseudomallei. With GSK3 beta inhibition, we found significant modulation between pro-(IL-12, TNF-alpha) and anti-inflammatory (IL-10) serum cytokines which may have contributed to bacterial clearance in multiple organs of B. pseudomallei-infected hyperglycaemic mice. Concurrently, an increase in phosphorylation of GSK3 beta at Ser-9 was observed in the liver of B. pseudomallei-infected hyperglycaemic mice. Likewise, B. pseudomallei-infected non-hyperglycaemic mice upon GSK3 beta inhibition showed similar trends of bacterial clearance and modulation of serum cytokines; however, the effect of enhanced survival was less substantial than in infected hyperglycaemic mice. Taken together, we demonstrate that inhibition of GSK3 beta confers survival advantage of hyperglycaemic mice infected with B. pseudomallei and offers a potential therapeutic strategy for the treatment of diabetic patients with melioidosis.

• 出版日期2018-3