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Volume 156, Issue 9

protein kinase K confers survival advantage during early infection in mice and regulates growth in culture and during persistent infection: implications for immune modulation Free

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.

  • Received:
  • Accepted:
  • Revised:
  • Published Online:
Keyword(s): ADS, albumin-dextrose-saline , BCG, Bacillus Calmette-Guérin , Ct, cycle threshold , HRP, horseradish peroxidase , IEM, immunoelectron microscopy , IFN, interferon , IL, interleukin , iNOS, inducible nitric oxide synthase , Mtb, Mycobacterium tuberculosis , qRT-PCR, quantitative RT-PCR , SCOTS, selective capture of transcribed sequences , SEM, scanning electron microscopy , STPK, serine/threonine protein kinase , TEM, transmission electron microscopy and TNF, tumour necrosis factor
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2010-09-01
2024-04-25
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Mycobacterium tuberculosis protein kinase K confers survival advantage during early infection in mice and regulates growth in culture and during persistent infection: implications for immune modulation
Microbiology 156, 2829 (2010); https://doi.org/10.1099/mic.0.040675-0
/content/journal/micro/10.1099/mic.0.040675-0
/content/journal/micro/10.1099/mic.0.040675-0
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