<i>Mycobacterium smegmatis</i>biofilm formation and sliding motility are affected by the serine/threonine protein kinase PknF

Narayanan, Sujatha; Jacobs, William R.; Av‐Gay, Yossef

doi:10.1111/j.1574-6968.2007.00989.x

Cited by 36 publications

(30 citation statements)

References 19 publications

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“…As shown in Fig. 5E, the wild type strains dispersed well on the surface of BM-2 plates (left panel), indicating that it has good motility, which is consistent with previous reports (23). In contrast, no obvious dispersion was observed for MsdisA overexpression strains, indicating that overexpression of MsdisA inhibited the motility of M. smegmatis (Fig.…”

Section: Overexpression Of Msdisa But Not Co-expression Of Msdisamsrsupporting

confidence: 91%

Radiation-sensitive Gene A (RadA) Targets DisA, DNA Integrity Scanning Protein A, to Negatively Affect Cyclic Di-AMP Synthesis Activity in Mycobacterium smegmatis

Zhang

2013

Journal of Biological Chemistry

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Background:Little is known about the control of cyclic di-AMP synthesis in bacteria. Results: RadA targets DisA to inhibit its cyclic di-AMP synthesis activity that regulates mycobacterial growth. Conclusion:We report a novel mechanism of control of c-di-AMP synthesis and its effects on bacterial growth in Mycobacterium smegmatis. Significance: These findings enhance our understanding of c-di-AMP synthesis control and its roles in bacteria.

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Section: Overexpression Of Msdisa But Not Co-expression Of Msdisamsrsupporting

confidence: 91%

Radiation-sensitive Gene A (RadA) Targets DisA, DNA Integrity Scanning Protein A, to Negatively Affect Cyclic Di-AMP Synthesis Activity in Mycobacterium smegmatis

Zhang

2013

Journal of Biological Chemistry

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“…Thus, previous studies have demonstrated that PknF can phosphorylate the FHA domains of two other proteins, Rv0020c and Rv1747 (16), and also the heat-shock protein GroEL1 (17). Furthermore, PknF has previously been implicated in regulating glucose uptake in M. tuberculosis (18), as well as in sliding motility and biofilm formation in Mycobacterium smegmatis (19). Thus, mycobacterial Ser/Thr protein kinases have been identified as promising therapeutic targets.…”

Section: Introductionmentioning

confidence: 99%

Forkhead-associated (FHA) Domain Containing ABC Transporter Rv1747 Is Positively Regulated by Ser/Thr Phosphorylation in Mycobacterium tuberculosis

Spivey

Molle

Whalan

et al. 2011

Journal of Biological Chemistry

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One major signaling method employed by Mycobacterium tuberculosis, the causative agent of tuberculosis, is through reversible phosphorylation of proteins mediated by protein kinases and phosphatases. This study concerns one of these enzymes, the serine/threonine protein kinase PknF, that is encoded in an operon with Rv1747, an ABC transporter that is necessary for growth of M. tuberculosis in vivo and contains two forkhead-associated (FHA) domains. FHA domains are phosphopeptide recognition motifs that specifically recognize phosphothreonine-containing epitopes. Experiments to determine how PknF regulates the function of Rv1747 demonstrated that phosphorylation occurs on two specific threonine residues, Thr-150 and Thr-208. To determine the in vivo consequences of phosphorylation, infection experiments were performed in bone marrow-derived macrophages and in mice using threonine-to-alanine mutants of Rv1747 that prevent specific phosphorylation and revealed that phosphorylation positively modulates Rv1747 function in vivo. The role of the FHA domains in this regulation was further demonstrated by isothermal titration calorimetry, using peptides containing both phosphothreonine residues. FHA-1 domain mutation resulted in attenuation in macrophages highlighting the critical role of this domain in Rv1747 function. A mutant deleted for pknF did not, however, have a growth phenotype in an infection, suggesting that other kinases can fulfill its role when it is absent. This study provides the first information on the molecular mechanism(s) regulating Rv1747 through PknF-dependent phosphorylation but also indicates that phosphorylation activates Rv1747, which may have important consequences in regulating growth of M. tuberculosis.

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“…Several studies have established that mycobacterial STPKs regulate a variety of metabolic processes, including cell shape and cell division (Chaba et al , 2002; Dasgupta et al , 2006, Kang et al , 2005, 2008; Thakur & Chakraborti, 2006, 2008), sugar uptake (Deol et al , 2005), metabolic enzymes (Molle et al , 2006; Veyron-Churlet et al , 2009), nitrogen homeostasis (Cowley et al , 2004; O'Hare et al , 2008), transcription (Cohen-Gonsaud et al , 2009; Greenstein et al , 2007; Kumar et al , 2009; Park et al , 2008; Sharma et al , 2006) and biofilm formation (Gopalaswamy et al , 2008). Despite such extensive research, very little is known about STPK expression and function during M. tuberculosis growth and survival in human macrophages.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2010

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Mycobacterium tuberculosis 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, pknD, pknG, pknH, pknJ, pknK and pknL, showed higher expression in H37Rv. In the second screen, STPK expression was analysed in H37Rv-infected human macrophages. Interestingly, significant expression of pknK was detected only at 18 h post-infection, suggesting its involvement in early infection events. We have investigated the roles of PknK in vitro and in vivo. PknK levels were induced under stationary phase and deletion of pknK resulted in increased resistance of the mutant to acidic pH, hypoxia, oxidative and stationary-phase stresses in vitro. These results, together with the increased survival of the ΔpknK 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 ΔpknK 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-γ 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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Mycobacterium smegmatisbiofilm formation and sliding motility are affected by the serine/threonine protein kinase PknF

Cited by 36 publications

References 19 publications

Radiation-sensitive Gene A (RadA) Targets DisA, DNA Integrity Scanning Protein A, to Negatively Affect Cyclic Di-AMP Synthesis Activity in Mycobacterium smegmatis

Radiation-sensitive Gene A (RadA) Targets DisA, DNA Integrity Scanning Protein A, to Negatively Affect Cyclic Di-AMP Synthesis Activity in Mycobacterium smegmatis

Forkhead-associated (FHA) Domain Containing ABC Transporter Rv1747 Is Positively Regulated by Ser/Thr Phosphorylation in Mycobacterium tuberculosis

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

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