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HlyIIR (Hemolysin II Regulator) is a transcriptional regulator of the gene for pore-forming toxin hemolysin II of Bacillus cereus.


Contents


Introduction

B. cereus is a Gram-positive, spore-forming bacterium, commonly found in soil or water. It is also found as a contaminant in food and pharmaceutical products.[1] [2] Some strains of this microorganism could caus emetic and enteric food-poisoning, periodontitis and systemic infections.[3] The pathogenic properties of B. cereus are determined by the production of several extracellular virulence factors.[4] Production of such toxins by bacterial cells is tightly controlled by different regulatory systems. [5][6] In particular, synthesis of pore-forming cytotoxin hemolysin II is controlled at the level of transcription by HlyIIR.[7][8]

Hemolysin II Regulator

The gene encoding HlyIIR (201 amino acid residues) is located immediately downstream of hemolysin II gene. The presence of HlyIIR decreases the level of hemolysin II expression in heterologous systems in vivo (Escherichia coli and B. subtilis). Purified HlyIIR protein also inhibited in vitro transcription from the promoter of hemolysin II gene. HlyIIR is a DNA-binding protein recognising a specific 44-bp region in hemolysin II gene promoter-operator segment. This segment is unusually organised, being a long perfect inverted repeat containing degenerate subrepeats. Two HlyIIR dimers non-cooperatively and independently bind to the operator with an apparent dissociation constant falling in a nanomolar range. Interestingly, mechanism of HlyIIR repression is not just a simple competition with RNA-polymerase (RNAP) for the promoter. HlyIIR forms a ternary complex with RNAP on the promoter of hemolysin II gene and represses transcription by inhibiting isomerisation of RNAP closed promoter complex into a catalytically active open promoter complex.


References

  1. Garcia Arribas ML, Plaza CJ, de la Rosa MC, Mosso MA. Characterization of Bacillus cereus strains isolated from drugs and evaluation of their toxins. J Appl Bacteriol. 1988 Mar;64(3):257-64. PMID:3133346
  2. Anderson Borge GI, Skeie M, Sorhaug T, Langsrud T, Granum PE. Growth and toxin profiles of Bacillus cereus isolated from different food sources. Int J Food Microbiol. 2001 Sep 28;69(3):237-46. PMID:11603861
  3. Lund T, De Buyser ML, Granum PE. A new cytotoxin from Bacillus cereus that may cause necrotic enteritis. Mol Microbiol. 2000 Oct;38(2):254-61. PMID:11069652
  4. Granum PE, Lund T. Bacillus cereus and its food poisoning toxins. FEMS Microbiol Lett. 1997 Dec 15;157(2):223-8. PMID:9435100
  5. Slamti L, Lereclus D. A cell-cell signaling peptide activates the PlcR virulence regulon in bacteria of the Bacillus cereus group. EMBO J. 2002 Sep 2;21(17):4550-9. PMID:12198157
  6. Harvie DR, Vilchez S, Steggles JR, Ellar DJ. Bacillus cereus Fur regulates iron metabolism and is required for full virulence. Microbiology. 2005 Feb;151(Pt 2):569-77. PMID:15699205 doi:151/2/569
  7. Budarina ZI, Nikitin DV, Zenkin N, Zakharova M, Semenova E, Shlyapnikov MG, Rodikova EA, Masyukova S, Ogarkov O, Baida GE, Solonin AS, Severinov K. A new Bacillus cereus DNA-binding protein, HlyIIR, negatively regulates expression of B. cereus haemolysin II. Microbiology. 2004 Nov;150(Pt 11):3691-701. PMID:15528656 doi:150/11/3691
  8. Rodikova EA, Kovalevskiy OV, Mayorov SG, Budarina ZI, Marchenkov VV, Melnik BS, Leech AP, Nikitin DV, Shlyapnikov MG, Solonin AS. Two HlyIIR dimers bind to a long perfect inverted repeat in the operator of the hemolysin II gene from Bacillus cereus. FEBS Lett. 2007 Mar 20;581(6):1190-6. Epub 2007 Feb 28. PMID:17346714 doi:10.1016/j.febslet.2007.02.035



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Oleg Kovalevskiy

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