Modified gram-negative bacteria for use as vaccines
The invention relates to Gram-negative bacteria carrying an inactivated gene encoding a glycosyltransferase involved in the synthesis of the core of the LPS of said Gram-negative bacteria, wherein said inactivated gene results in the synthesis of a LPS having a modified core. These strains have an attenuated virulence but induce a humoral immunity sufficient for ensuring vaccination of the host.
1. A method for the treatment of brucellosis, comprising the step of administering to a subject in need thereof a therapeutically effective amount of a gram-negative bacterium carrying an inactivated gene encoding a glycosyltransferase involved in the synthesis of the core of the LPS of said gram-negative bacterium,
wherein said glycosyltransferase has the amino acid sequence of SEQ ID NO:1,
wherein said inactivated gene encoding a glycosyltransferase involved in the synthesis of the core of the LPS of said Gram-negative bacterium results in the synthesis of a LPS having a modified core and wherein said Gram-negative bacterium is of the genus Brucella.
2. The method according to claim 1 , wherein a gene encoding a protein involved in the synthesis of the O-polysaccharide of the LPS is inactivated.
3. The method according to claim 2 , wherein said protein involved in the synthesis of the O-polysaccharide of the LPS is a perosamine synthetase having the amino acid sequence of SEQ ID NO:13.
4. The method according to claim 1 , wherein said bacteria of the genus Brucella is selected from the group consisting of the bacteria of the species Brucella melitensis, Brucella abortus, Brucella suis, Brucella ovis, Brucella pinnipedialis, Brucella ceti, Brucella microti , and Brucella canis.
5. The method according to claim 1 , wherein said bacteria of the genus Brucella is of the species Brucella abortus.