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A novel anti-virulence gene revealed by proteomic analysis in Shigella flexneri 2a

DOI: 10.1186/1477-5956-8-30

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Abstract:

The ArgT protein was dramatically down-regulated at 37 degrees C. In contrast, the ArgT from the non-pathogenic E. coli did not show this differential expression as in S. flexneri, which suggested that argT might be a potential anti-virulence gene. Competitive invasion assays in HeLa cells and in BALB/c mice with argT mutants were performed, and the results indicated that the over-expression of ArgTY225D would attenuate the virulence of S. flexneri. A comparative proteomic analysis was subsequently performed to investigate the effects of ArgT in S. flexneri at the molecular level. We show that HtrA is differentially expressed among different derivative strains.Gene argT is a novel anti-virulence gene that may interfere with the virulence of S. flexneri via the transport of specific amino acids or by affecting the expression of the virulence factor, HtrA.Shigella flexneri is a gram-negative, facultative pathogen that is the leading cause of communicable bacterial dysenteries in developing countries. The virulence genes of S. flexneri are located on a large plasmid that was acquired by horizontal gene transfer. These genes encode a type III secretion system (TTSS) apparatus that enables S. flexneri to invade epithelial cells in the lower gut of humans [1].The expression of virulence genes is induced under growth conditions similar to those found at the site of invasion. For example, a temperature of 37°C is a particularly important environmental signal. Maurelli et al. [2] found that S. flexneri cultivated at 37°C produced kerato-conjunctivitis in guinea pigs and were able to penetrate and replicate in intestinal epithelial cells, but that bacteria grown at 30°C were phenotypically avirulent and noninvasive. Other studies in S. flexneri have focused on regulation of the expression of these virulence genes at different temperatures [1,3]. However, we expected that, in addition to known virulence genes, a large number of other genes would be differentially expressed in

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