According to the WHO, typhoid fever remains a serious public health problem throughout the world, with an estimated 16-33 million cases and 500,000 to 600,000 deaths annually. The Vi capsule of S. typhi, the causative agent of typhoid fever, is a surface-bound carbohydrate polymer to which antibodies have been shown to protect against typhoid fever. Purification of this polymer from virulent S. typhi strains poses a danger to those handling the live organisms. However, an unusual strain of Citrobacter freundii, WR7004, was mutated by the inventors to create a strain (WR7011) that makes Vi polysaccharide on its surface. Specifically, the strain was mutated using nitrosoguanidine. C. freundii WR7011 makes several times as much Vi polysaccharide as strains of S. typhi, is nonpathogenic, and is much safer to work with for Vi production or use as a vaccine strain. The inventors anticipate that this strain of C. freundii will reduce costs of purifying the Vi polysaccharide and also provide an increased level of safety during manufacture of the polysaccharide.
Potential Commercial Applications:
Synthesis of S. typhi Vi polysaccharide.
De Qi Xu
Research Tool -- patent protection is not be pursued for this technology
NJ Snellings et al. Genetic regulation of variable Vi antigen expression in a strain of Citrobacter freundii. J Bacteriol. 1981 Feb;145(2):1010-1017. PubMed abs
H-S Houng et al. Expression of Vi antigen in Escherichia coli K-12: characterization of ViaB from Citrobacter freundii and identity of ViaA with RcsB. J Bacteriol. 1992 Sep;174(18):5910-5915. PubMed abs
JT Ou et al. Specific insertion and deletion of insertion sequence 1-like DNA element causes the reversible expression of the virulent capsular antigen Vi of Citrobacter freundii in Escherichia coli. Proc Natl Sci USA. 1988 June;85(12):4402-4405. PubMed abs
SC Szu et al. Vi capsular polysaccharide-protein conjugates for prevention of typhoid fever. J Exp Med. 1987 Nov 1;166(5):1510-24. PubMed abs
The FDA-CBER Laboratory of Enteric and Sexually Transmitted Diseases is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize Vi polysaccharide from Citrobacter freundii. Please contact Dr. Dennis J. Kopecko at 301-496-1893 or (firstname.lastname@example.org) for more information.
Bill Ronnenberg, JD-MIP, MS
FDA Technology Transfer Program
10903 New Hampshire Ave.
Building WO1, Rm 4214
Silver Spring, MD 20993
OTT Reference No: E-004-2007/0
Updated: August 9, 2015