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Export of the Virulence Factors from Shigella Flexneri and Characterization of the mxi loci
Uniformed Services University Of The Health Sciences Bethesda United States
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Virulence of Shigella flexneri requires a 220 kilobase kb plasmid which encodes temperature-regulated genes necessary for early steps in Shigella pathogenesis. To identify temperature-regulated virulence genes on the plasmid, lacZ protein fusions were randomly generated in S. flexneri and screened for fusions to temperature-regulated promoters. Analysis of one non-invasive mutant revealed that it made wild-type intracellular levels of invasion plasmid antigens Ipa but was deficient in their export. Furthermore. an analysis of cellular fractions showed that the normally excreted Ipa gene products were absent in the outer membrane of the mutant. Thus, export of these antigens to the extracellular environment is essential for Shigella virulence. The locus defined by this mutant was designated mxiA. The mxiA product was characterized as a 76 kilodalton kDa polypeptide homologous to the inner membrane regulatory protein of the low calcium response locus, LcrD, of Yersinia pestis, which is implicated in the export of Yersinia antigens. Thus, MxiA, a homolog of LcrD, may function either by directly affecting the excretion of virulence factors or by regulating expression of accessory genes of a multi-component protein export system. An additional locus, mxiC, encoding a 40 kDa putative cytoplasmic protein, was identified upstream of mxiA. Homology searches revealed no similarities between mxiC and any known prokaryotic gene. A mutation in this locus conferred the Mxi- phenotype and was found to affect virulence of S. flexneri at the level of invasion, which correlated with reduced excretion of IpaC.
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