Physiological consequences associated with overproduction of Mycobacterium tuberculosis FtsZ in mycobacterial hosts

Dziadek, Jarosław; Madiraju, Murty V. V. S.; Rutherford, Stacey A.; Atkinson, Mark A.; Rajagopalan, Malini

doi:10.1099/00221287-148-4-961

Cited by 63 publications

(90 citation statements)

References 43 publications

(38 reference statements)

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“…To gain insights into the cell division process in mycobacteria, we began characterizing M. tuberculosis ftsZ (ftsZ tb ) expressed from heterologous promoters. We showed that in M. tuberculosis, expression of ftsZ tb from the ami promoter (amip) in a replicating vector did not result in a consistent level of expression whereas that from the Mycobacterium avium dnaA promoter led to non-viability (Dziadek et al, 2002). In contrast, viable M. smegmatis transformants producing consistent levels of FtsZ tb were obtained with both plasmids.…”

Section: Introductionmentioning

confidence: 84%

“…Mycobacterium smegmatis. The cell division process in M. smegmatis is also not well understood (Dziadek et al, 2002;Gomez & Bishai, 2000). Although the project to determine the nucleotide sequence of M. smegmatis is not complete, its genome appears to contain homologues of all annotated M. tuberculosis cell division genes [see http:// www.tigr.org/tdb/mdb/mdbinprogress.html (Dziadek et al, 2002)].…”

Section: Introductionmentioning

confidence: 99%

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Conditional expression of Mycobacterium smegmatis ftsZ, an essential cell division gene

et al. 2003

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To understand the role of Mycobacterium smegmatis ftsZ (ftsZ smeg ) in the cell division process, the ftsZ gene was characterized at the genetic level. This study shows that ftsZ smeg is an essential gene in that it can only be disrupted in a merodiploid background carrying another functional copy. Expression of ftsZ smeg in M. smegmatis from a constitutively active mycobacterial promoter resulted in lethality whereas that from a chemically inducible acetamidase (ami ) promoter led to FtsZ accumulation, filamentation and cell lysis. To further understand the roles of ftsZ in cell division a conditionally complementing ftsZ smeg mutant strain was constructed in which ftsZ expression is controlled by acetamide. Growth in the presence of 0?2 % acetamide increased FtsZ levels approximately 1?4-fold, but did not decrease viability or change cell length. Withdrawal of acetamide reduced FtsZ levels, decreased viability, increased cell length and eventually lysed the cells. Finally, it is shown that ftsZ smeg function in M. smegmatis can be replaced with the Mycobacterium tuberculosis counterpart, indicating that heterologous FtsZ tb can independently initiate the formation of Z-rings and catalyse the septation process. It is concluded that optimal levels of M. smegmatis FtsZ are required to sustain cell division and that the cell division initiation mechanisms are similar in mycobacteria.

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Section: Introductionmentioning

confidence: 84%

Section: Introductionmentioning

confidence: 99%

Conditional expression of Mycobacterium smegmatis ftsZ, an essential cell division gene

et al. 2003

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“…When calculated, ϳ12,000 MtrB molecules/ M. tuberculosis cell were found. Slightly lower levels (ϳ7500 molecules) of MtrB were found in M. smegmatis, which grows more rapidly, with an average doubling time of 3 h. We reported earlier that the intracellular levels of FtsZ, MtrA, and CrgA proteins in M. tuberculosis correspond to 30,000, 4,000, and 20,000 molecules/actively growing cell, respectively (8,20,21). Thus, MtrB appears to be a relatively abundant protein in M. tuberculosis.…”

Section: Mtrb Is An Abundant Protein That Localizes To Cell Polesmentioning

confidence: 99%

Septal Localization of the Mycobacterium tuberculosis MtrB Sensor Kinase Promotes MtrA Regulon Expression

Plocinska

Gorla

Sarva

et al. 2012

Journal of Biological Chemistry

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103

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Background:The MtrB sensor kinase is a component of the essential MtrAB signal transduction system. Results: MtrB localizes to septa independent of phosphorylation; MtrB septal association and phosphorylation are necessary for cell division and expression of MtrA targets. Conclusion: MtrB septal localization and MtrA-regulon expression are linked. Significance: MtrB septal assembly triggers the activation of the MtrAB signal transduction pathway.

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“…Preparation of cellular lysates of M. tuberculosis by bead-beating and Western blotting protocols were as described (Dziadek et al, 2002). Known amounts of cellular lysates based on the equivalent protein concentration were resolved by SDS-PAGE, transferred to Protran nitrocellulose membranes (Schleicher and Schuell).…”

Section: Preparation Of Cellular Lysates and Western Blottingmentioning

confidence: 99%

Modulation of Mycobacterium tuberculosis proliferation by MtrA, an essential two‐component response regulator

Fol

Chauhan

Nair

et al. 2006

Molecular Microbiology

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SummaryPaired two-component regulatory systems consisting of a sensor kinase and a response regulator are the major means by which bacteria sense and respond to different stimuli. The role of essential response regulator, MtrA, in Mycobacterium tuberculosis proliferation is unknown. We showed that elevating the intracellular levels of MtrA prevented M. tuberculosis from multiplying in macrophages, mice lungs and spleens, but did not affect its growth in broth. Intracellular trafficking analysis revealed that a vast majority of MtrA overproducing merodiploids were associated with lysosomal associated membrane protein (LAMP-1) positive vacuoles, indicating that intracellular growth attenuation is, in part, due to an impaired ability to block phagosome-lysosome fusion. A merodiploid strain producing elevated levels of phosphorylation-defective MtrA (MtrA D53N ) was partially replicative in macrophages, but was attenuated in mice. Quantitative real-time PCR analyses revealed that expression of dna A, an essential replication gene, was sharply upregulated during intramacrophage growth in the MtrA overproducer in a phosphorylation-dependent manner. Chromatin immunoprecipitation using anti-MtrA antibodies provided direct evidence that MtrA regulator binds to dna A promoter in vivo indicating that dna A promoter is a MtrA target. Simultaneous overexpression of mtr A regulator and its cognate mtr B kinase neither inhibited growth nor sharply increased the expression levels of dna A in macrophages. We propose that proliferation of M. tuberculosis in vivo depends, in part, on the optimal ratio of phosphorylated to nonphosphorylated MtrA response regulator.

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Physiological consequences associated with overproduction of Mycobacterium tuberculosis FtsZ in mycobacterial hosts

Cited by 63 publications

References 43 publications

Conditional expression of Mycobacterium smegmatis ftsZ, an essential cell division gene

Conditional expression of Mycobacterium smegmatis ftsZ, an essential cell division gene

Septal Localization of the Mycobacterium tuberculosis MtrB Sensor Kinase Promotes MtrA Regulon Expression

Modulation of Mycobacterium tuberculosis proliferation by MtrA, an essential two‐component response regulator

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