P. Helena Mäkelä

ANTIGENIC SIMILARITIES BETWEEN BRAIN COMPONENTS AND BACTERIA CAUSING MENINGITIS: Implications for Vaccine Development and Pathogenesis

Glycopeptides containing polysialic acid units were isolated from human and rat brain and tested for reactivity with antibodies against meningococcal capsules. The polysialosyl glycopeptides bound specifically to horse antiserum against meningococcus group B. The interaction was inhibited by capsular polysaccharides from meningococcus group B but not groups A or C. The capsular polysaccharide of Escherichia coli K1, which is immunochemically similar to the group B polysaccharide, also inhibited binding. These findings could explain the failure to develop efficient vaccines against group B meningococcus or E coli K1 and also suggest that immunological tolerance could be a factor in the pathogenesis of meningitis caused by these bacteria. The presence of the cross-reactive brain component calls for caution in efforts to develop capsular polysaccharide vaccines from these bacteria or the proposed use of passively administered antibodies as immunotherapy of neonatal meningitis.

MANNOSE-RESISTANT HAEMAGGLUTINATION AND P ANTIGEN RECOGNITION ARE CHARACTERISTIC OF ESCHERICHIA COLI CAUSING PRIMARY PYELONEPHRITIS

Thirty-two Escherichia coli strains from 30 children with pyelonephritis were examined for their haemagglutination patterns and O and K serotypes. 29 (91%) of the strains showed mannose-resistant haemagglutination (MRHA). By use of well-defined target cells, these MRHA+ strains could be shown to recognise human cells either in a P-specific manner (recognising a specific galactosyl-galactose structure which is part of P blood groups antigens) or in a separate, X-specific manner. Both recognition mechanisms could occur separately or together on the same bacteria, the frequencies of P and X specificity being 81 and 19%, respectively. Both MRHA and P specificity were significantly associated with the O antigens 01, 04, 06, 016, and 018, and the capsular antigen K1, which have previously been associated with pyelonephritis. However, the association of MRHA and P specificity with upper urinary tract infection in children is greater than that of any other laboratory-defined bacterial characteristic.

Genetic aspects of biosynthesis and structure of Salmonella somatic polysaccharide.

The genetic approach has proved valuable in the investigation of the structure of the complex somatic polysaccharide of Salmonella LPS, because a variant unable to effect some biochemical reaction involved in the biosynthesis of wild-type somatic polysaccharide makes an abnormaI LPS, with a polysaccharide component simpler than that of the wild-type form. These simplified LPS and polysaccharides have proved useful both for analysis of structure and as substrates in experiments on their in vitro and in vivo conversion into complete-or more nearly complete-structures. The genetic control of the structure of Salmonella somatic polysaccharide is of special interest to the microbial geneticist, among other reasons because of the unusually great differences in chemical structure (and by inference in equipment of the relevant biosynthetic enzymes and of genes controlling them) between Salmonella of different 0 groups, which are yet capable of hybridization. Other writers in this monograph have discussed the phenomenon of 0-antigen conversion by phages. We shall consider the changes in somatic polysaccharide constitution which result either from mutation in a single strain or from recombination between wild-type strains of different 0 groups. In Salmonella of various species, conjugation and genetic recombination of two strains can be achieved by mixing a “female” (gene-acceptor) strain with a strain made into a “male” or gene-donor strain by the use of either colicine factors (Ozeki and Howarth, 1961; Smith and Stocker, 1962; Subbaiah and Stocker, 1964) or of the F factor, integrated into the chromosome of an Hfr strain (Makela, 1963, 1965; Sanderson and Demerec, 1965). By analysis of their pattern of segregation among recombinants from such crosses, it has been shown that all the genes of Salmonella, as of Escherichia coli, can be ordered in a single circular linkage map, corresponding (it is thought) to a closed-loop chromosome or DNA molecule. Genes responsible for particular features of the structure of somatic polysaccharide can be mapped in this way. In the interpretation of the results, it is assumed:

GENETIC HOMOLOGIES BETWEEN FLAGELLAR ANTIGENS OF ESCHERICHIA COLI AND SALMONELLA ABONY.

SUMMARY: Genes determining the flagellar antigens were introduced from Hfr Salmonella abony into F− Escherichia coli by sexual recombination. The gene H1 for the phase-1 flagellar antigen of Salmonella was found to be allelic to H, the gene for the only flagellar antigen of E. coli. The phase-2 antigen of Salmonella has no counterpart in E. coli; if the corresponding salmonella gene H2 is introduced in E. coli, diphasic strains are produced whose phase-2 antigen is that of the Salmonella parent; the phase-1 antigen can be that of either parent. In each case the diphasic strains undergo a true phase variation, with either the phase-1 or the phase-2 antigen being expressed at one time. The rates of this variation are comparable to those in the Salmonella parent.