A wbpP gene encoding a putative UDP-N-acetyl-D-glucosamine C 4 epimerase was identified and cloned from Vibrio vulnificus. The functions of the wbpP gene, assessed by the construction of an isogenic mutant and by evaluating its phenotype changes, demonstrated that WbpP is essential in both the pathogenesis and the capsular polysaccharide biosynthesis of V. vulnificus.The pathogenic marine bacterium Vibrio vulnificus is a causative agent of food-borne diseases, such as life-threatening septicemia and possibly gastroenteritis, in individuals with underlying predisposing conditions (8,17,31). Surface polysaccharides, such as capsular polysaccharides (CPS) and lipopolysaccharides, play crucial roles in the pathogenicity of gramnegative bacteria by assisting the bacteria to evade host defenses. CPS production is believed to be a major virulence factor of V. vulnificus that is essential for pathogenicity (8,17,31). Encapsulated strains of V. vulnificus that are virulent in mice have opaque colony morphologies on an agar surface, whereas acapsular transposon mutants are no longer virulent and appear translucent (34). Meanwhile, partially encapsulated V. vulnificus translucent-phase variants fall between the fully encapsulated wild type and acapsular transposon mutants in terms of their virulence and serum resistance (33, 34), thereby indicating that the amount of CPS on the cell surface correlates positively with the virulence of V. vulnificus.However, very little is known about the biosynthetic pathway for the capsular polysaccharide of V. vulnificus, and the genes encoding the enzymes involved in the production of the capsular polysaccharide have not yet been identified. Nonetheless, it is generally believed that a similar biosynthetic pathway operates in gram-negative bacteria. Thus, the biosynthetic pathways and molecular genetics of surface polysaccharide production have been widely studied in Pseudomonas aeruginosa (1). The common glycolytic metabolite glucose 1-phosphate is first converted to UDP-N-acetyl-D-glucosamine (UDPGlcNAc), the main activated precursor of surface-associated carbohydrate synthesis (1, 5). UDP-N-acetyl-D-galactosamine (UDP-GalNAc) is then formed by the C 4 epimerization of UDP-GlcNAc (5). UDP-N-acetyl-D-galactosaminuronic acid (UDP-GalNAcA), the product of the further dehydrogenation of UDP-GalNAc, is an important intermediate used for the biosynthesis of different uronic acid sugars of surface polysaccharides that contain GalNAcA or its derivatives, not only in P. aeruginosa, but also in other organisms (36). Also, it has been recently reported that the epimerization is performed by the gene products of wbpP (1).So far, a great diversity of capsular types have been presented among different isolates of V. vulnificus, and more than 13 CPS chemotypes were identified by chromatographic analysis and nuclear magnetic resonance spectroscopy (9). Yet, compared with the substantial body of literature concerned with the structural determination of the CPS from V. vulnificus (4,9,24,25), only a few...