GSK3β inhibition confers survival advantage in Burkholderia pseudomallei-infected hyperglycaemic mice by regulating inflammatory response

P. Maniam, M. Kalimutho, Mohammed Noor Embi, Hasidah Mohd. Sidek

Research output: Contribution to journalArticle

Abstract

Burkholderia pseudomallei, the etiologic agent of melioidosis is a common cause of sepsis mainly in diabetic individuals in South East Asia. Glycogen synthase kinase-3β (GSK3β) plays a pivotal role in modulating inflammatory balance in Gram-negative bacterial infections. In this study, we demonstrate that inhibition of GSK3β significantly improved survival of hyperglycaemic mice acutely infected with B. pseudomallei. With GSK3β 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 GSK3β at Ser-9 was observed in the liver of B. pseudomallei-infected hyperglycaemic mice. Likewise, B. pseudomallei-infected non-hyperglycaemic mice upon GSK3β 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 GSK3β confers survival advantage of hyperglycaemic mice infected with B. pseudomallei and offers a potential therapeutic strategy for the treatment of diabetic patients with melioidosis.

Original languageEnglish
Pages (from-to)228-238
Number of pages11
JournalTropical Biomedicine
Volume35
Issue number1
Publication statusPublished - 1 Jan 2018

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Burkholderia pseudomallei
Glycogen Synthase Kinase 3
Obese Mice
Survival
Melioidosis
Gram-Negative Bacterial Infections
Cytokines
Far East
Interleukin-12
Serum
Interleukin-10
Sepsis
Anti-Inflammatory Agents
Tumor Necrosis Factor-alpha
Phosphorylation
Liver
Therapeutics

ASJC Scopus subject areas

  • Parasitology
  • Infectious Diseases

Cite this

GSK3β inhibition confers survival advantage in Burkholderia pseudomallei-infected hyperglycaemic mice by regulating inflammatory response. / Maniam, P.; Kalimutho, M.; Embi, Mohammed Noor; Mohd. Sidek, Hasidah.

In: Tropical Biomedicine, Vol. 35, No. 1, 01.01.2018, p. 228-238.

Research output: Contribution to journalArticle

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