Study of the role of Mce3R on the transcription of mce genes of Mycobacterium tuberculosis

Santangelo, María de la Paz; Blanco, Federico Carlos; Bianco, María Verónica; Klepp, Laura I.; Zábal, Osvaldo; Cataldi, Angel; Bigi, Fabiana

doi:10.1186/1471-2180-8-38

Cited by 43 publications

(41 citation statements)

References 29 publications

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“…These findings suggest that, in addition to the mce3 operon and mce3R, which are already known to be under Mce3R regulation (Santangelo et al, 2002(Santangelo et al, , 2008, the expression of the Rv1936-Rv1941 and Rv1933c-Rv1935c loci is directly regulated by the binding of Mce3R to the operator motifs identified.…”

Section: Identification Of the Mce3r Binding Motifsmentioning

confidence: 81%

“…The construction of the Dmce3R mutant is described by Santangelo et al (2008). All cloning steps were performed in Escherichia coli DH5a.…”

Section: Methodsmentioning

confidence: 99%

“…Cells were then harvested by centrifugation and resuspended in 100 mM Tris/HCl, pH 7.5, 1 M NaCl, 20 % glycerol, 1 % NP-40 and 0.5 mM PMSF. Soluble cell extracts from the cultures were prepared as described elsewhere (Santangelo et al, 2008) and His-Mce3R recombinant protein was purified from the supernatants by using Ni + resin (Ni-NTA agarose, Qiagen), following the manufacturer's recommendation (Invitrogen).…”

Section: Methodsmentioning

confidence: 99%

“…We have found that this regulation is specific for the mce3 operon (among all the mce genes) and that the Mce3R repressor regulates its own expression (Santangelo et al, 2008). In this study, we investigated additional genes that are regulated by Mce3R in order to define the Mce3R regulon.…”

Section: Introductionmentioning

confidence: 99%

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Mce3R, a TetR-type transcriptional repressor, controls the expression of a regulon involved in lipid metabolism in Mycobacterium tuberculosis

Santangelo¹,

Klepp²,

Nuñéz-García

et al. 2009

Microbiology

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The mce operons constitute four homologous regions in the Mycobacterium tuberculosis genome, each of which has 8-13 ORFs. Although the function of the Mce protein family has not been clearly established, its members are believed to be membrane lipid transporters. Based on functional experiments, we found that the regulator of the mce3 locus, Mce3R, negatively regulates the expression of the Rv1933c-Rv1935c and Rv1936-Rv1941 transcriptional units. These operons are adjacent to one another and divergently transcribed. The predicted functions of most of these genes are related to either lipid metabolism or redox reactions. Bioinformatic analysis of the 59 UTR sequences of the differentially expressed genes allowed us to define a putative Mce3R motif. Importantly, the Mce3R motif was present six and three times in the mce3R-yrbE3A and Rv1935c-Rv1936 intergenic regions, respectively. Two occurrences of this motif mapped within the two regions of the mce3 operon that were protected by Mce3R in a footprinting analysis, thus indicating that this motif is likely to serve as an operator site for the Mce3R regulator in the promoter. In addition, alterations in the lipid content of M. tuberculosis were detected in the absence of Mce3R. Taken together, these results suggest that Mce3R controls the expression of both the putative transport system encoded in the mce3 operon and the enzymes implicated in the modification of the Mce3-transported substrates.

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Section: Identification Of the Mce3r Binding Motifsmentioning

confidence: 81%

“…The construction of the Dmce3R mutant is described by Santangelo et al (2008). All cloning steps were performed in Escherichia coli DH5a.…”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Mce3R, a TetR-type transcriptional repressor, controls the expression of a regulon involved in lipid metabolism in Mycobacterium tuberculosis

Santangelo¹,

Klepp²,

Nuñéz-García

et al. 2009

Microbiology

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“…FadR regulators are the most abundant amongst the GntR family of transcription regulators and consist of all a-helical C-terminal domains with a mean length of~160 aa (Haydon & Guest, 1991;Rigali et al, 2002;Vindal et al, 2007a, b). Extensive studies have been carried on the FadRs of Escherichia coli, Vibrio vulnificus and Corynebacterium glutamicum, and they are reported to play important roles both in cellular physiology and virulence (Agari et al, 2011;Brown & Gulig, 2008;Casali et al, 2006;Georgi et al, 2008;Santangelo et al, 2008). However, current knowledge on the promoter architecture and regulation of these FadR-like proteins in mycobacteria is limited.…”

Section: Introductionmentioning

confidence: 99%

Rv0494 is a starvation-inducible, auto-regulatory FadR-like regulator from Mycobacterium tuberculosis

et al. 2015

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Fatty acid metabolism plays an important role in the survival and pathogenesis of Mycobacterium tuberculosis. Lipids are assumed to be the major source of energy during dormancy. Here, we report the characterization of a starvation-inducible, lipid-responsive transcriptional regulator, Rv0494, divergently transcribed from the Rv0493c probable operon. The striking difference in the transcriptional regulatory apparatus between mycobacteria and other well-studied organisms, such as Escherichia coli, is the organization of mycobacterial promoters. Mycobacterial promoters have diverse architectures and most of these promoters function inefficiently in E. coli. In this study, we characterized the promoter elements of Rv0494 along with the sigma factors required for transcription initiation. Rv0494 promoter activity increased under nutrient starvation conditions and was transcribed via two promoters: the promoter proximal to the translational start site was active under standard growth conditions, whilst both promoters contributed to the increased activity seen during starvation, with the major contribution from the distal promoter. Furthermore, Rv0494 translation initiated at a codon located 9 bp downstream of the annotated start codon. Rv0494 bound to its upstream sequence to auto-regulate its own expression; this binding was responsive to long-chain fatty acyl-CoA molecules. We further report Rv0494-mediated transcriptional regulation of the Rv2326c gene -a probable transmembrane ATP-binding transporter encoding gene.

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More than cholesterol catabolism: regulatory vulnerabilities in Mycobacterium tuberculosis

Bonds

Sampson

2018

Current Opinion in Chemical Biology

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Mycobacterium tuberculosis (Mtb) is the epitome of persistent. Mtb is the pathogen that causes tuberculosis, the leading cause of death by infection worldwide. The success of this pathogen is due in part to its clever ability to adapt to its host environment and its effective manipulation of the host immune system. A major contributing factor to the survival and virulence of Mtb is its acquisition and metabolism of host derived lipids including cholesterol. Accumulating evidence suggests that the catabolism of cholesterol during infection is highly regulated by cholesterol catabolites. We review what is known about how regulation interconnects with cholesterol catabolism. This framework provides support for an indirect approach to drug development that targets Mtb cholesterol metabolism through dysregulation of nutrient utilization pathways.

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Study of the role of Mce3R on the transcription of mce genes of Mycobacterium tuberculosis

Cited by 43 publications

References 29 publications

Mce3R, a TetR-type transcriptional repressor, controls the expression of a regulon involved in lipid metabolism in Mycobacterium tuberculosis

Mce3R, a TetR-type transcriptional repressor, controls the expression of a regulon involved in lipid metabolism in Mycobacterium tuberculosis

Rv0494 is a starvation-inducible, auto-regulatory FadR-like regulator from Mycobacterium tuberculosis

More than cholesterol catabolism: regulatory vulnerabilities in Mycobacterium tuberculosis

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