1887

Abstract

serine/threonine protein kinases (STPKs) are key regulators of growth and metabolism; however, evidence for their roles in virulence is limited. In a preliminary screen based on comparative expression between strains H37Rv and H37Ra, six STPK genes, , , , , and , showed higher expression in H37Rv. In the second screen, STPK expression was analysed in H37Rv-infected human macrophages. Interestingly, significant expression of was detected only at 18 h post-infection, suggesting its involvement in early infection events. We have investigated the roles of PknK and . PknK levels were induced under stationary phase and deletion of resulted in increased resistance of the mutant to acidic pH, hypoxia, oxidative and stationary-phase stresses . These results, together with the increased survival of the Δ strain during persistent infection in mice, reveal a role for PknK in adaptive mechanisms that slow the growth of mycobacteria. A novel finding of this study was the inhibition of growth of Δ strain during acute infection in mice that correlated with the significant upregulation of tumour necrosis factor as well as the simultaneous downregulation of interleukin-12p40, interferon- and induced nitric oxide synthase transcripts. Finally, we provide evidence for the localization of PknK during infection and discuss its implications in pathogenesis.

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2010-09-01
2020-04-10
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