CONTRIBUTION OF GENES FROM THE CAPSULE GENE-COMPLEX (CPS) TO LIPOOLIGOSACCHARIDE BIOSYNTHESIS AND SERUM RESISTANCE IN NEISSERIA-MENINGITIDIS

Within the capsule gene complex (cps) of Neisseria meningitidis B a 5. 5 kb DNA fragment encodes proteins with strong homologies to enzymes o f the lipopolysaccharide biosynthetic pathway of Salmonella typhimuriu m and Escherichia coli, GalE, RfbB, RfbC and RfbD. A meningococcal gal E mutant expressed a truncated lipooligosaccharide (LOS), which termin ated at the glucose residue between inner and outer core, and a second galE gene present outside the cps cluster was found to be transcripti onally and functionally inactive and, thus, unable to complement this defect. Because of the defect in the outer core, the LOS of the galt-d efective meningococcal mutant was not sialylated. In contrast, carbohy drate analysis of the LOS of an rfb-defective meningococcal mutant rev ealed no difference from the LOS of the wild-type strain, suggesting t hat the rfb genes are inactive. This was supported by Northern blot an alysis, which showed that expression of the rfb gene products was tran scriptionally regulated. The inability of the meningococcal galE mutan t, which cannot sialylate the LOS, allowed us to investigate the signi ficance of LOS sialylation in relation to the presence of the polysial ic acid capsule. Sialylated LOS, but not the polysialic acid capsule, is necessary to confer complete serum resistance on the meningococcus by inhibition of the alternative complement pathway.