Disease relevance of virB

• Deregulation of temperature-dependent transcription of the invasion regulatory gene, virB, in Shigella by rho mutation [1].
• Autoinducer 2 (AI-2), a quorum signaling molecule active in late log phase, was synthesized by Shigella species and enteroinvasive Escherichia coli and shown to be responsible for the observed peak of virB expression [2].
• The expression of listeriolysin, a major virulence factor of the gram-positive facultative intracellular pathogen Listeria monocytogenes, is positively regulated by a transcriptional activator, the prfA gene product [3].

High impact information on virB

• The role of promoter curvature as thermosensor is also compatible with the present observation that, with increasing temperature, the virF bending centre moves downstream at a rate having its maximum around the transition temperature, abruptly unmasking a binding site for the transcriptional activator FIS [4].
• We conclude that tRNA modification, temperature and superhelicity have the same target - the expression of VirF - to influence the expression of the central regulatory gene virB and thereby the virulence of Shigella [5].
• The expression of virA was under the control of the virB gene, the positive regulator of the ipa, mxi and spa operons [6].
• Expression of the virB gene, the transcriptional regulator for the invasion genes encoded by the large plasmid of Shigella flexneri, is temperature-regulated. virB transcription is under the control of VirF and H-NS, which act as positive and negative regulators, respectively, and is highly responsive to changes in DNA superhelicity [1].
• These results indicated that Rho protein could have a profound effect on topological temperature-dependent changes in DNA structure, thus contributing to thermoregulation of virB transcription [1].

Chemical compound and disease context of virB

• A strategy to identify asymmetric binding sites is presented and applied to locate potential binding sites upstream of other genes that Rns can activate, including those encoding the CS2 and CFA/I pili of enterotoxigenic E. coli and the global regulator virB of Shigella flexneri [7].

Biological context of virB

• The gene (designated virB) was identified and its nucleotide sequence determined [8].
• The expression of ipa genes is regulated positively by virF through the activation of virB on the plasmid [9].
• On the other hand, transcriptions of ipa and the other two inv operons depended on the activation of virB transcription but not on temperature [9].
• The deregulation of virB expression by the mutation was dependent upon the virB promoter, since the effects of the mutation on virB transcription were abolished when its promoter region was replaced by the tac promoter [1].
• The virF and virB loci encode regulatory proteins required for transcriptional activation of the virulence regulon [10].

Associations of virB with chemical compounds

• Furthermore, when the mutant was grown in medium containing novobiocin, an inhibitor of DNA gyrase, virB transcription at 30 degrees C as well as at 37 degrees C was greatly diminished [1].
• Polyacrylamide gel electrophoresis of three DNA fragments containing the virF, the virB and the VirG promoters demonstrates, in agreement with computer predictions, that they have an intrinsically curved structure, confirming the preference of H-NS for bent DNA [11].

Regulatory relationships of virB

• It acts as a transcriptional activator and is itself transcriptionally activated by another virulence protein, VirF [12].

Other interactions of virB

• The previously reported regulatory activity of the virF gene some 30 kb distance away was shown to act exclusively through virB [8].
• In contrast, the activation of the virG gene necessary for intercellular spread occurred directly by virF without the requirement for virB [8].
• These results indicate that virA is a new member of the invasion regulon directed by virB and that the VirA function is involved in invasion and intercellular spreading [6].
• The ipaJ gene encodes a 780 bp open reading frame (ORF), separated from the ipaR (virB) stop codon by 944 bp [13].
• These results indicated that a reduction of virB transcription, which is known to occur in the pINV-integrated strain HN280/32, accounts for reduced apyrase expression and that the histone-like protein H-NS is involved in this regulatory network [14].

Analytical, diagnostic and therapeutic context of virB

• Multiplex PCR analysis of DNA obtained from spontaneous avirulent derivatives indicated that virF and virB were deleted or otherwise inactivated in over 97% of the isolates [10].
• DNA footprinting analysis indicated that the VirF fusion and H-NS proteins bound to the upstream sequence spanning from -17 to -117 and to the sequence from -20 to +20, in which virB transcription starts, respectively [15].

References