Molecular Interaction of the Shigella Flexneri Protein H-NS and Its Significance in the Temperature Regulation of Virulence
Uniformed Services University Of The Health Sciences Bethesda United States
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Shigella flexneri is an enteric pathogen and the causative agent of bacillary dysentery. Virulence is regulated by many environmental signals, although temperature is thought to be the primary signal. Virulence gene expression is repressed at 30 degrees C and induced at 37 degrees C. The regulatory cascade begins with the antagonistic relationship between H-NS, a negative regulator of virB. and VirF, a positive regulator of virB. The C-terminal portion of the HNS protein binds to the curved DNA sequence upstream of the virB promoter inhibiting access to VirF and the RNA polymerase at 30 degrees C. At 37 degrees C, VirF binds upstream of virBand positively regulates virB transcription. Subsequently, VirB activates transcription ofthe virulence genes for attachment and invasion, encoded on the 220 kb plasmid. The significance of H-NS is its inhibition of transcription of the virulence genes at temperatures 37 degrees C allowing the bacterium to conserve energy when not inside a mammalian host. In this thesis, the role of H-NS as a global regulator in the bacterial cell is explored in relation to Shigella virulence gene expression and other stress-induced genes.