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an important global regulator controlling the production ofnumerous virulence factors such as capsular polysaccharidesin bacterial pathogens. The nucleotide and deduced aminoacid sequences of smcR, a homolog of V. harveyi luxRidentified from V. vulnificus ATCC29307, were analyzed. Theamino acid sequence of SmcR from V. vulnificus was 72 to92% similar to those of LuxR homologs from Vibrio spp.isogenic mutant, whose smcR gene was inactivated by alelicexchanges, and by evaluating its phenotype changes in vitroand in mice. The disruption of smcR resulted in a significantalteration in biofilm formation, in type of colony morphology,and in motility. When compared with the wild-type, thesmcR mutant exhibited reduced survival under adverseconditions, such as acidic pH and hyperosmotic stress. ThesmcR mutant exhibited decreased cytotoxic activity towardin vitro. Furthermore, the intraperitoneal LD50of the smcR mutant was approximately 102 times higher thanthat of parental wild-type. Therefore, it apears that SmcRis a novel global regulator, controling numerous genescontributing to the pathogenesis as wel as survival of V.vulnificus.