Frameshifting by transcriptional slippage is involved in production of MxiE, the transcription activator regulated by the activity of the type III secretion apparatus in Shigella flexneri

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Abstract
Bacteria of Shigella spp. are responsible for shigellosis in humans. They use a type III secretion (TTS) system encoded by a 200 kb virulence plasmid to enter epithelial cells and trigger apoptosis in macrophages. This TTS system comprises a secretion apparatus, translocators and effectors that transit through this apparatus, cytoplasmic chaperones and specific transcription regulators. The TTS apparatus assembled during growth of Shigella flexneri in broth is activated upon contact with epithelial cells. Transcription of approximately 15 genes encoding effectors, including IpaH proteins, is regulated by the TTS apparatus activity and controlled by MxiE, a transcription activator of the AraC family, and IpgC, the chaperone of the translocators IpaB and IpaC. We present evidence that MxiE is produced by a frameshift between a 59-codon open reading frame (ORF) (mxiEa) containing the translation start site and a 214-codon ORF (mxiEb) encoding the DNA binding domain of the protein. The mxiEa encoded N-terminal part of MxiE is required for MxiE function. Frameshifting efficiency was approximately 30% during growth in broth and was not modulated by the activity of secretion or the coactivator IpgC. Frameshifting involves slippage of RNA polymerase during transcription of mxiE, which results in the incorporation of one additional nucleotide in the mRNA and places mxiEa and mxiEb in the same reading frame. Frameshifting might represent an additional means of controlling gene expression under specific environmental conditions.