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

Abstract

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.

Genome sequence comparisons of serial multi-drug-resistant Mycobacterium tuberculosis isolates over 21 years of infection in a single patient

“…Between February 2002 and June 2003, a nucleotide insertion occurred causing a frameshift mutation in Rv2623c, a putative ABC transporter ATP-binding protein ( Yousuf et al , 2015 ). Expression of the transcriptional regulator Rv0494 is increased in M. tuberculosis during conditions of starvation such as during dormancy ( Yousuf et al , 2015 ). Furthermore, Rv0494 has been shown to downregulate expression of Rv2623c ( Yousuf et al , 2015 ).…”

“…Expression of the transcriptional regulator Rv0494 is increased in M. tuberculosis during conditions of starvation such as during dormancy ( Yousuf et al , 2015 ). Furthermore, Rv0494 has been shown to downregulate expression of Rv2623c ( Yousuf et al , 2015 ). This suggests that latency is associated with decreased expression of Rv2623c.…”

Mycobacterial Metabolic Syndrome: LprG and Rv1410 Regulate Triacylglyceride Levels, Growth Rate and Virulence in Mycobacterium tuberculosis

“…For example, FFA act as regulatory molecules in E . coli lipid biosynthesis [ 60 ] and recent data suggest that FFA regulate lipid synthesis by regulating fatty acid synthase (FasI) in both mycobacteria and corynebacteria [ 48 , 61 , 62 ]. FFA have also recently been shown to bind transcription factors that regulate the MmpL family of transporters, some of which transport specific classes of outer membrane lipids and are also associated with lipid biosynthesis [ 63 ].…”

GeNET: a web application to explore and share Gene Co-expression Network Analysis data

“…4B ). These three TFs have previously been implicated in regulation of hypoxia, starvation and/or virulence in M. tuberculosis ( Abomoelak et al, 2009 ; Bretl et al, 2012 ; Yousuf et al, 2015 ). The magenta module is the only module enriched with targets of all these three TFs.…”