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The Mycobacterium Tuberculosis PhoPR Operon is Positively Autoregulated in the Virulent Strain H37Rv

Overview
Journal J Bacteriol
Specialty Microbiology
Date 2008 Sep 2
PMID 18757548
Citations 28
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Abstract

The attenuated Mycobacterium tuberculosis H37Ra strain is an isogenic counterpart of the virulent paradigm strain H37Rv. Recently, a link between a point mutation in the PhoP transcriptional regulator and avirulence of H37Ra was established. Remarkably, a previous study demonstrated negative autoregulation of the phoP gene in H37Ra. These findings led us to study the transcriptional autoregulation of PhoP in the virulent H37Rv strain. In contrast to the negative autoregulation of PhoP previously published for H37Ra, our experiments using a phoP promoter-lacZ fusion showed that PhoP is positively autoregulated in both H37Rv and H37Ra compared with an H37Rv phoP deletion mutant constructed in this study. Using quantitative reverse transcription-PCR (RT-PCR) analysis, we showed that the phoP gene is transcribed at similar levels in H37Rv and H37Ra. Gel mobility shift and DNase I footprinting assays allowed us to identify the precise binding region of PhoP from H37Rv to the phoP promoter. We also carried out RT-PCR studies to demonstrate that phoP is transcribed together with the adjacent gene phoR, which codes for the cognate histidine kinase of the phoPR two-component system. In addition, quantitative RT-PCR studies showed that phoR is independently transcribed from a promoter possibly regulated by PhoP. Finally, we discuss the possible role in virulence of a single point mutation found in the phoP gene from the attenuated H37Ra strain but not in virulent members of the M. tuberculosis complex.

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References
1.
Perez E, Samper S, Bordas Y, Guilhot C, Gicquel B, Martin C . An essential role for phoP in Mycobacterium tuberculosis virulence. Mol Microbiol. 2001; 41(1):179-87. DOI: 10.1046/j.1365-2958.2001.02500.x. View

2.
Gupta S, Sinha A, Sarkar D . Transcriptional autoregulation by Mycobacterium tuberculosis PhoP involves recognition of novel direct repeat sequences in the regulatory region of the promoter. FEBS Lett. 2006; 580(22):5328-38. DOI: 10.1016/j.febslet.2006.09.004. View

3.
Campoy S, Fontes M, Padmanabhan S, Cortes P, Llagostera M, Barbe J . LexA-independent DNA damage-mediated induction of gene expression in Myxococcus xanthus. Mol Microbiol. 2003; 49(3):769-81. DOI: 10.1046/j.1365-2958.2003.03592.x. View

4.
Rodriguez-Garcia A, Ludovice M, Martin J, Liras P . Arginine boxes and the argR gene in Streptomyces clavuligerus: evidence for a clear regulation of the arginine pathway. Mol Microbiol. 1997; 25(2):219-28. DOI: 10.1046/j.1365-2958.1997.4511815.x. View

5.
Asensio J, Maia C, Ferrer N, Barilone N, Laval F, Soto C . The virulence-associated two-component PhoP-PhoR system controls the biosynthesis of polyketide-derived lipids in Mycobacterium tuberculosis. J Biol Chem. 2005; 281(3):1313-6. DOI: 10.1074/jbc.C500388200. View