Brucella spp. are Gram-negative bacteria that behave as facultative intracellular parasites of a variety of mammals. This genus includes smooth (S) and rough (R) species that carry S and R lipopolysaccharides (LPS), respectively. S-LPS is a virulence factor, and mutants affected in the S-LPS O-polysaccharide (R mutants), core oligosaccharide or both show attenuation. However,
B. ovis is naturally R and is virulent in sheep. We studied the role of
B. ovis LPS in virulence by mutating the orthologues of
wadA,
wadB and
wadC, three genes known to encode LPS core glycosyltransferases in S brucellae. When mapped with antibodies to outer membrane proteins (Omps) and R-LPS,
wadB and
wadC mutants displayed defects in LPS structure and outer membrane topology but inactivation of
wadA had little or no effect. Consistent with these observations, the
wadB and
wadC but not the
wadA mutants were attenuated in mice. When tested as vaccines, the
wadB and
wadC mutants protected mice against
B. ovis challenge. The results demonstrate that the LPS core is a structure essential for survival in vivo not only of S brucellae but also of a naturally R
Brucella pathogenic species, and they confirm our previous hypothesis that the
Brucella LPS core is a target for vaccine development. Since vaccine
B. melitensis Rev 1 is S and thus interferes in serological testing for S brucellae,
wadB mutant represents a candidate vaccine to be evaluated against
B. ovis infection of sheep suitable for areas free of
B. melitensis.
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