|
|
||||||||
Molecular Genetics and Immunobiology of Mycobacteria |
Department of Infectious Diseases and Microbiology, Centre for Molecular Microbiology and Infection, Imperial College of Science Technology and Medicine, London SW7 2AZ, UK1
School of Crystallography, Birkbeck College, University of London, Malet Street, London WC1E 7HX, UK2
Department of Medical Microbiology, St Georges Hospital Medical School, Cranmer Terrace, London SW17 0RE, UK3
Author for correspondence: Graham Stewart. Tel: +44 207 594 3090. Fax: +44 207 594 3095. e-mail: g.stewart{at}ic.ac.uk
Regulation of the expression of heat-shock proteins plays an important role in the pathogenesis of Mycobacterium tuberculosis. The heat-shock response of bacteria involves genome-wide changes in gene expression. A combination of targeted mutagenesis and whole-genome expression profiling was used to characterize transcription factors responsible for control of genes encoding the major heat-shock proteins of M. tuberculosis. Two heat-shock regulons were identified. HspR acts as a transcriptional repressor for the members of the Hsp70 (DnaK) regulon, and HrcA similarly regulates the Hsp60 (GroE) response. These two specific repressor circuits overlap with broader transcriptional changes mediated by alternative sigma factors during exposure to high temperatures. Several previously undescribed heat-shock genes were identified as members of the HspR and HrcA regulons. A novel HspR-controlled operon encodes a member of the low-molecular-mass
-crystallin family. This protein is one of the most prominent features of the M. tuberculosis heat-shock response and is related to a major antigen induced in response to anaerobic stress.
Keywords: HspR, HrcA, Hsp70, Hsp60, transcriptional regulator
Abbreviations: ADC, albumin/dextrose (glucose)/catalase; CIRCE, controlling inverted repeat of chaperone expression; HAIR, HspR-associated inverted repeat; OADC, oleic acid/dextrose (glucose)/albumin/catalase
a A list of the 100 ORFs most highly induced by heat shock is provided as supplementary data with the online version of this paper (http://mic.sgmjournals.org).
This article has been cited by other articles:
![]() |
S. Mehra and D. Kaushal Functional Genomics Reveals Extended Roles of the Mycobacterium tuberculosis Stress Response Factor {sigma}H J. Bacteriol., June 15, 2009; 191(12): 3965 - 3980. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. Krawczyk, T. A. Kohl, A. Goesmann, J. Kalinowski, and J. Baumbach From Corynebacterium glutamicum to Mycobacterium tuberculosis--towards transfers of gene regulatory networks and integrated data analyses with MycoRegNet Nucleic Acids Res., June 3, 2009; (2009) gkp453v1. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Ehira, H. Teramoto, M. Inui, and H. Yukawa Regulation of Corynebacterium glutamicum Heat Shock Response by the Extracytoplasmic-Function Sigma Factor SigH and Transcriptional Regulators HspR and HrcA J. Bacteriol., May 1, 2009; 191(9): 2964 - 2972. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. C. Garcia Pelayo, S. Uplekar, A. Keniry, P. Mendoza Lopez, T. Garnier, J. Nunez Garcia, L. Boschiroli, X. Zhou, J. Parkhill, N. Smith, et al. A Comprehensive Survey of Single Nucleotide Polymorphisms (SNPs) across Mycobacterium bovis Strains and M. bovis BCG Vaccine Strains Refines the Genealogy and Defines a Minimal Set of SNPs That Separate Virulent M. bovis Strains and M. bovis BCG Strains Infect. Immun., May 1, 2009; 77(5): 2230 - 2238. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. J. Canova, L. Kremer, and V. Molle The Mycobacterium tuberculosis GroEL1 Chaperone Is a Substrate of Ser/Thr Protein Kinases J. Bacteriol., April 15, 2009; 191(8): 2876 - 2883. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. Provvedi, F. Boldrin, F. Falciani, G. Palu, and R. Manganelli Global transcriptional response to vancomycin in Mycobacterium tuberculosis Microbiology, April 1, 2009; 155(4): 1093 - 1102. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. Barreiro, D. Nakunst, A. T. Huser, H. D. de Paz, J. Kalinowski, and J. F. Martin Microarray studies reveal a 'differential response' to moderate or severe heat shock of the HrcA- and HspR-dependent systems in Corynebacterium glutamicum Microbiology, February 1, 2009; 155(2): 359 - 372. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. L. Smollett, A. S. Fivian-Hughes, J. E. Smith, A. Chang, T. Rao, and E. O. Davis Experimental determination of translational start sites resolves uncertainties in genomic open reading frame predictions - application to Mycobacterium tuberculosis Microbiology, January 1, 2009; 155(1): 186 - 197. [Abstract] [Full Text] [PDF] |
||||
![]() |
B. R. G. Gordon, R. Imperial, L. Wang, W. W. Navarre, and J. Liu Lsr2 of Mycobacterium Represents a Novel Class of H-NS-Like Proteins J. Bacteriol., November 1, 2008; 190(21): 7052 - 7059. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. H. Li, W. L. Lam, and R. W. Stokes Characterization of genes differentially expressed within macrophages by virulent and attenuated Mycobacterium tuberculosis identifies candidate genes involved in intracellular growth Microbiology, August 1, 2008; 154(8): 2291 - 2303. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. M. Chen, H. Ren, J. E. Shaw, Y. J. Wang, M. Li, A. S. Leung, V. Tran, N. M. Berbenetz, D. Kocincova, C. M. Yip, et al. Lsr2 of Mycobacterium tuberculosis is a DNA-bridging protein Nucleic Acids Res., April 1, 2008; 36(7): 2123 - 2135. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. Das Gupta, B. Bandyopadhyay, and S. K. Das Gupta Modulation of DNA-binding activity of Mycobacterium tuberculosis HspR by chaperones Microbiology, February 1, 2008; 154(2): 484 - 490. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. Fontan, V. Aris, S. Ghanny, P. Soteropoulos, and I. Smith Global Transcriptional Profile of Mycobacterium tuberculosis during THP-1 Human Macrophage Infection Infect. Immun., February 1, 2008; 76(2): 717 - 725. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. Rengarajan, E. Murphy, A. Park, C. L. Krone, E. C. Hett, B. R. Bloom, L. H. Glimcher, and E. J. Rubin Mycobacterium tuberculosis Rv2224c modulates innate immune responses PNAS, January 8, 2008; 105(1): 264 - 269. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. L. Williams, T. L. Pittman, M. Deshotel, S. Oby-Robinson, I. Smith, and R. Husson Molecular Basis of the Defective Heat Stress Response in Mycobacterium leprae J. Bacteriol., December 15, 2007; 189(24): 8818 - 8827. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. R. Campbell, K. E. Chapman, K. J. Waldron, S. Tottey, S. Kendall, G. Cavallaro, C. Andreini, J. Hinds, N. G. Stoker, N. J. Robinson, et al. Mycobacterial Cells Have Dual Nickel-Cobalt Sensors: SEQUENCE RELATIONSHIPS AND METAL SITES OF METAL-RESPONSIVE REPRESSORS ARE NOT CONGRUENT J. Biol. Chem., November 2, 2007; 282(44): 32298 - 32310. [Abstract] [Full Text] [PDF] |
||||
![]() |
C.-w. Wu, S. K. Schmoller, S. J. Shin, and A. M. Talaat Defining the Stressome of Mycobacterium avium subsp. paratuberculosis In Vitro and in Naturally Infected Cows J. Bacteriol., November 1, 2007; 189(21): 7877 - 7886. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. Golby, K. A. Hatch, J. Bacon, R. Cooney, P. Riley, J. Allnutt, J. Hinds, J. Nunez, P. D. Marsh, R. G. Hewinson, et al. Comparative transcriptomics reveals key gene expression differences between the human and bovine pathogens of the Mycobacterium tuberculosis complex Microbiology, October 1, 2007; 153(10): 3323 - 3336. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. S. Milne, S. L. Michell, H. Diaper, P. Wikstrom, K. Svensson, P. C. F. Oyston, and R. W. Titball A 55 kDa hypothetical membrane protein is an iron-regulated virulence factor of Francisella tularensis subsp. novicida U112 J. Med. Microbiol., October 1, 2007; 56(10): 1268 - 1276. [Abstract] [Full Text] [PDF] |
||||
![]() |
X. Pang and S. T. Howard Regulation of the {alpha}-Crystallin Gene acr2 by the MprAB Two-Component System of Mycobacterium tuberculosis J. Bacteriol., September 1, 2007; 189(17): 6213 - 6221. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. J. V. Beste, E. Laing, B. Bonde, C. Avignone-Rossa, M. E. Bushell, and J. J. McFadden Transcriptomic Analysis Identifies Growth Rate Modulation as a Component of the Adaptation of Mycobacteria to Survival inside the Macrophage J. Bacteriol., June 1, 2007; 189(11): 3969 - 3976. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Sato, K. Nimura-Matsune, S. Watanabe, T. Chibazakura, and H. Yoshikawa Expression Analysis of Multiple dnaK Genes in the Cyanobacterium Synechococcus elongatus PCC 7942 J. Bacteriol., May 15, 2007; 189(10): 3751 - 3758. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. Brosch, S. V. Gordon, T. Garnier, K. Eiglmeier, W. Frigui, P. Valenti, S. Dos Santos, S. Duthoy, C. Lacroix, C. Garcia-Pelayo, et al. Genome plasticity of BCG and impact on vaccine efficacy PNAS, March 27, 2007; 104(13): 5596 - 5601. [Abstract] [Full Text] [PDF] |
||||
![]() |
V. Hughes, S. Smith, A. Garcia-Sanchez, J. Sales, and K. Stevenson Proteomic comparison of Mycobacterium avium subspecies paratuberculosis grown in vitro and isolated from clinical cases of ovine paratuberculosis Microbiology, January 1, 2007; 153(1): 196 - 206. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. E. Geiman, T. R. Raghunand, N. Agarwal, and W. R. Bishai Differential Gene Expression in Response to Exposure to Antimycobacterial Agents and Other Stress Conditions among Seven Mycobacterium tuberculosis whiB-Like Genes. Antimicrob. Agents Chemother., August 1, 2006; 50(8): 2836 - 2841. [Abstract] [Full Text] [PDF] |
||||
![]() |
G. W. Buchko, C.-Y. Kim, T. C. Terwilliger, and M. A. Kennedy Solution Structure of the Conserved Hypothetical Protein Rv2302 from Mycobacterium tuberculosis. J. Bacteriol., August 1, 2006; 188(16): 5993 - 6001. [Abstract] [Full Text] [PDF] |
||||
![]() |
B. Henderson, E. Allan, and A. R. M. Coates Stress Wars: the Direct Role of Host and Bacterial Molecular Chaperones in Bacterial Infection Infect. Immun., July 1, 2006; 74(7): 3693 - 3706. [Full Text] [PDF] |
||||
![]() |
D. Patel, L. Danelishvili, Y. Yamazaki, M. Alonso, M. L. Paustian, J. P. Bannantine, L. Meunier-Goddik, and L. E. Bermudez The Ability of Mycobacterium avium subsp. paratuberculosis To Enter Bovine Epithelial Cells Is Influenced by Preexposure to a Hyperosmolar Environment and Intracellular Passage in Bovine Mammary Epithelial Cells. Infect. Immun., May 1, 2006; 74(5): 2849 - 2855. [Abstract] [Full Text] [PDF] |
||||
![]() |
O. Musatovova, S. Dhandayuthapani, and J. B. Baseman Transcriptional Heat Shock Response in the Smallest Known Self-Replicating Cell, Mycoplasma genitalium. J. Bacteriol., April 1, 2006; 188(8): 2845 - 2855. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. He, R. Hovey, J. Kane, V. Singh, and T. C. Zahrt MprAB Is a Stress-Responsive Two-Component System That Directly Regulates Expression of Sigma Factors SigB and SigE in Mycobacterium tuberculosis J. Bacteriol., March 15, 2006; 188(6): 2134 - 2143. [Abstract] [Full Text] [PDF] |
||||
![]() |
Y. Hu, F. Movahedzadeh, N. G. Stoker, and A. R. M. Coates Deletion of the Mycobacterium tuberculosis {alpha}-Crystallin-Like hspX Gene Causes Increased Bacterial Growth In Vivo Infect. Immun., February 1, 2006; 74(2): 861 - 868. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. M. Chen, G. J. German, D. C. Alexander, H. Ren, T. Tan, and J. Liu Roles of Lsr2 in Colony Morphology and Biofilm Formation of Mycobacterium smegmatis J. Bacteriol., January 15, 2006; 188(2): 633 - 641. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. Brodin, L. Majlessi, L. Marsollier, M. I. de Jonge, D. Bottai, C. Demangel, J. Hinds, O. Neyrolles, P. D. Butcher, C. Leclerc, et al. Dissection of ESAT-6 System 1 of Mycobacterium tuberculosis and Impact on Immunogenicity and Virulence Infect. Immun., January 1, 2006; 74(1): 88 - 98. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Ventura, Z. Zhang, M. Cronin, C. Canchaya, J. G. Kenny, G. F. Fitzgerald, and D. van Sinderen The ClgR Protein Regulates Transcription of the clpP Operon in Bifidobacterium breve UCC 2003 J. Bacteriol., December 15, 2005; 187(24): 8411 - 8426. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Ventura, G. F. Fitzgerald, and D. van Sinderen Genetic and Transcriptional Organization of the clpC Locus in Bifidobacterium breve UCC 2003 Appl. Envir. Microbiol., October 1, 2005; 71(10): 6282 - 6291. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. K. Kennaway, J. L. P. Benesch, U. Gohlke, L. Wang, C. V. Robinson, E. V. Orlova, H. R. Saibi, and N. H. Keep Dodecameric Structure of the Small Heat Shock Protein Acr1 from Mycobacterium tuberculosis J. Biol. Chem., September 30, 2005; 280(39): 33419 - 33425. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Ventura, J. G. Kenny, Z. Zhang, G. F. Fitzgerald, and D. van Sinderen The clpB gene of Bifidobacterium breve UCC 2003: transcriptional analysis and first insights into stress induction Microbiology, September 1, 2005; 151(9): 2861 - 2872. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. K. Schmid, H. A. Howell, J. R. Battista, S. N. Peterson, and M. E. Lidstrom Global Transcriptional and Proteomic Analysis of the Sig1 Heat Shock Regulon of Deinococcus radiodurans J. Bacteriol., May 15, 2005; 187(10): 3339 - 3351. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. N. Murphy, G. R. Stewart, V. V. Mischenko, A. S. Apt, R. Harris, M. S. B. McAlister, P. C. Driscoll, D. B. Young, and B. D. Robertson The OtsAB Pathway Is Essential for Trehalose Biosynthesis in Mycobacterium tuberculosis J. Biol. Chem., April 15, 2005; 280(15): 14524 - 14529. [Abstract] [Full Text] [PDF] |
||||
![]() |
G. S. Hotter, B. J. Wards, P. Mouat, G. S. Besra, J. Gomes, M. Singh, S. Bassett, P. Kawakami, P. R. Wheeler, G. W. de Lisle, et al. Transposon Mutagenesis of Mb0100 at the ppe1-nrp Locus in Mycobacterium bovis Disrupts Phthiocerol Dimycocerosate (PDIM) and Glycosylphenol-PDIM Biosynthesis, Producing an Avirulent Strain with Vaccine Properties At Least Equal to Those of M. bovis BCG J. Bacteriol., April 1, 2005; 187(7): 2267 - 2277. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. A. Wilkinson, G. R. Stewart, S. M. Newton, H. M. Vordermeier, J. R. Wain, H. N. Murphy, K. Horner, D. B. Young, and R. J. Wilkinson Infection Biology of a Novel {alpha}-Crystallin of Mycobacterium tuberculosis: Acr2 J. Immunol., April 1, 2005; 174(7): 4237 - 4243. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. J. V. Beste, J. Peters, T. Hooper, C. Avignone-Rossa, M. E. Bushell, and J. McFadden Compiling a Molecular Inventory for Mycobacterium bovis BCG at Two Growth Rates: Evidence for Growth Rate-Mediated Regulation of Ribosome Biosynthesis and Lipid Metabolism J. Bacteriol., March 1, 2005; 187(5): 1677 - 1684. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. L. Tran, M. Rao, C. Simmers, S. Gebhard, K. Olsson, and G. M. Cook Mutants of Mycobacterium smegmatis unable to grow at acidic pH in the presence of the protonophore carbonyl cyanide m-chlorophenylhydrazone Microbiology, March 1, 2005; 151(3): 665 - 672. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. T. Andersen, L. Brondsted, B. M. Pearson, F. Mulholland, M. Parker, C. Pin, J. M. Wells, and H. Ingmer Diverse roles for HspR in Campylobacter jejuni revealed by the proteome, transcriptome and phenotypic characterization of an hspR mutant Microbiology, March 1, 2005; 151(3): 905 - 915. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. Qamra and S. C. Mande Crystal Structure of the 65-Kilodalton Heat Shock Protein, Chaperonin 60.2, of Mycobacterium tuberculosis J. Bacteriol., December 1, 2004; 186(23): 8105 - 8113. [Abstract] [Full Text] [PDF] |
||||
![]() |
N. M. Parrish, C. G. Ko, M. A. Hughes, C. A. Townsend, and J. D. Dick Effect of n-octanesulphonylacetamide (OSA) on ATP and protein expression in Mycobacterium bovis BCG J. Antimicrob. Chemother., October 1, 2004; 54(4): 722 - 729. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. Rajakumar, J. Shafi, R. J. Smith, R. A. Stabler, P. W. Andrew, D. Modha, G. Bryant, P. Monk, J. Hinds, P. D. Butcher, et al. Use of Genome Level-Informed PCR as a New Investigational Approach for Analysis of Outbreak-Associated Mycobacterium tuberculosis Isolates J. Clin. Microbiol., May 1, 2004; 42(5): 1890 - 1896. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. Manganelli, R. Proveddi, S. Rodrigue, J. Beaucher, L. Gaudreau, and I. Smith {sigma} Factors and Global Gene Regulation in Mycobacterium tuberculosis J. Bacteriol., February 15, 2004; 186(4): 895 - 902. [Full Text] [PDF] |
||||
![]() |
T. Stefanova, M. Chouchkova, J. Hinds, P. D. Butcher, J. Inwald, J. Dale, S. Palmer, R. G. Hewinson, and S. V. Gordon Genetic Composition of Mycobacterium bovis BCG Substrain Sofia J. Clin. Microbiol., November 1, 2003; 41(11): 5349 - 5349. [Full Text] [PDF] |
||||
![]() |
D. Schnappinger, S. Ehrt, M. I. Voskuil, Y. Liu, J. A. Mangan, I. M. Monahan, G. Dolganov, B. Efron, P. D. Butcher, C. Nathan, et al. Transcriptional Adaptation of Mycobacterium tuberculosis within Macrophages: Insights into the Phagosomal Environment J. Exp. Med., September 2, 2003; 198(5): 693 - 704. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Mogk, C. Schlieker, K. L. Friedrich, H.-J. Schonfeld, E. Vierling, and B. Bukau Refolding of Substrates Bound to Small Hsps Relies on a Disaggregation Reaction Mediated Most Efficiently by ClpB/DnaK J. Biol. Chem., August 15, 2003; 278(33): 31033 - 31042. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. Inwald, J. Hinds, S. Palmer, J. Dale, P. D. Butcher, R. G. Hewinson, and S. V. Gordon Genomic Analysis of Mycobacterium tuberculosis Complex Strains Used for Production of Purified Protein Derivative J. Clin. Microbiol., August 1, 2003; 41(8): 3929 - 3932. [Abstract] [Full Text] [PDF] |
||||
![]() |
I. Smith Mycobacterium tuberculosis Pathogenesis and Molecular Determinants of Virulence Clin. Microbiol. Rev., July 1, 2003; 16(3): 463 - 496. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. Parish, D. A. Smith, G. Roberts, J. Betts, and N. G. Stoker The senX3-regX3 two-component regulatory system of Mycobacterium tuberculosis is required for virulence Microbiology, June 1, 2003; 149(6): 1423 - 1435. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. B. Young Mycobacteria research in the post-genomic era Microbiology, October 1, 2002; 148(10): 2915 - 2917. [Full Text] [PDF] |
||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| INT J SYST EVOL MICROBIOL | MICROBIOLOGY | J GEN VIROL |
| J MED MICROBIOL | ALL SGM JOURNALS | |