<scp>GarA</scp> is an essential regulator of metabolism in <i><scp>M</scp>ycobacterium tuberculosis</i>

Ventura, Marcello; Rieck, Barbara; Boldrin, Francesca; Degiacomi, Giulia; Bellinzoni, M.; Barilone, Nathalie; Alzaidi, Faisal; Alzari, Pedro M.; Manganelli, Riccardo; O’Hare, Helen M.

doi:10.1111/mmi.12368

Cited by 59 publications

(66 citation statements)

References 36 publications

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“…In this system, the tetracycline repressor protein TetR is transcribed constitutively. It represses pip transcription in the absence of anhydrotetracycline (Ventura et al, 2013). When anhydrotetracycline is added, it binds to TetR, allowing transcription of pip which prevents transcription of integrated sepF MSMEG .…”

Section: Mycobacteria Protein Fragment Complementation (M-pfc)mentioning

confidence: 99%

Essential protein SepF of mycobacteria interacts with FtsZ and MurG to regulate cell growth and division

et al. 2015

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Section: Mycobacteria Protein Fragment Complementation (M-pfc)mentioning

confidence: 99%

Essential protein SepF of mycobacteria interacts with FtsZ and MurG to regulate cell growth and division

et al. 2015

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“…This dependency on Rho is remarkable for two reasons, the first being that inactivation of Rho reduced CFU by five orders of magnitude within a week. For comparison, genetic inactivation of many other attractive targets for drug development only decreased CFU by three orders of magnitude or less over a similar time period34454647484950. Second, not all genes required for growth are required for non-replicating persistence and drugs, for example INH, which is cidal for growing bacteria, can be virtually inactive against non-replicating bacteria.…”

Section: Discussionmentioning

confidence: 99%

Depleting Mycobacterium tuberculosis of the transcription termination factor Rho causes pervasive transcription and rapid death

et al. 2017

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Rifampicin, which inhibits bacterial RNA polymerase, provides one of the most effective treatments for tuberculosis. Inhibition of the transcription termination factor Rho is used to treat some bacterial infections, but its importance varies across bacteria. Here we show that Rho of Mycobacterium tuberculosis functions to both define the 3′ ends of mRNAs and silence substantial fragments of the genome. Brief inactivation of Rho affects over 500 transcripts enriched for genes of foreign DNA elements and bacterial virulence factors. Prolonged inactivation of Rho causes extensive pervasive transcription, a genome-wide increase in antisense transcripts, and a rapid loss of viability of replicating and non-replicating M. tuberculosis in vitro and during acute and chronic infection in mice. Collectively, these data suggest that inhibition of Rho may provide an alternative strategy to treat tuberculosis with an efficacy similar to inhibition of RNA polymerase.

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“…Further insight regarding the functions of PknG emerged with the identification of its primary substrate, the FHA domain-containing protein GarA (Rv1827), and the role of GarA in regulating central metabolic pathways ( 67 ). O'Hare and colleagues first demonstrated three phosphorylation sites in the amino-terminal region of PknG ( 19 ).…”

Section: Pkngmentioning

confidence: 99%

Mycobacterium tuberculosis Serine/Threonine Protein Kinases

Prisic

Husson

2014

Microbiol Spectr

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The Mycobacterium tuberculosis genome encodes 11 serine/threonine protein kinases (STPKs). A similar number of two-component systems are also present, indicating that these two signal transduction mechanisms are both important in the adaptation of this bacterial pathogen to its environment. The M. tuberculosis phosphoproteome includes hundreds of Ser- and Thr-phosphorylated proteins that participate in all aspects of M. tuberculosis biology, supporting a critical role for the STPKs in regulating M. tuberculosis physiology. Nine of the STPKs are receptor type kinases, with an extracytoplasmic sensor domain and an intracellular kinase domain, indicating that these kinases transduce external signals. Two other STPKs are cytoplasmic and have regulatory domains that sense changes within the cell. Structural analysis of some of the STPKs has led to advances in our understanding of the mechanisms by which these STPKs are activated and regulated. Functional analysis has provided insights into the effects of phosphorylation on the activity of several proteins, but for most phosphoproteins the role of phosphorylation in regulating function is unknown. Major future challenges include characterizing the functional effects of phosphorylation for this large number of phosphoproteins, identifying the cognate STPKs for these phosphoproteins, and determining the signals that the STPKs sense. Ultimately, combining these STPK-regulated processes into larger, integrated regulatory networks will provide deeper insight into M. tuberculosis adaptive mechanisms that contribute to tuberculosis pathogenesis. Finally, the STPKs offer attractive targets for inhibitor development that may lead to new therapies for drug-susceptible and drug-resistant tuberculosis.

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GarA is an essential regulator of metabolism in Mycobacterium tuberculosis

Cited by 59 publications

References 36 publications

Essential protein SepF of mycobacteria interacts with FtsZ and MurG to regulate cell growth and division

Essential protein SepF of mycobacteria interacts with FtsZ and MurG to regulate cell growth and division

Depleting Mycobacterium tuberculosis of the transcription termination factor Rho causes pervasive transcription and rapid death

Mycobacterium tuberculosis Serine/Threonine Protein Kinases

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