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H Lomberg

Publications and source records attributed to H Lomberg.

31 records · Page 2Linked to original sources

Influence of blood group on the availability of receptors for attachment of uropathogenic Escherichia coli.

Escherichia coli strains with defined receptor specificity were used as probes to analyze the individual variation in host cell receptors with respect to blood groups. The adhesins were initially characterized as mannose sensitive (MS), mannose resistant (MR), or nonagglutinating (-). The receptor specificity of the strains with MR adhesins was defined by agglutination of synthetic Gal alpha 1----4Gal beta covalently linked via a spacer arm, (CH2)2S(CH2)2CO approximately H-bovine serum albumin (BSA) to BSA-latex beads as specific for the globoseries glycolipid receptors (MR:GS). Strains with MR adhesins not reacting with Gal alpha 1----4Gal beta-BSA-latex were designated MR:nonGS. The attachment and hemagglutination of the MR:GS strains was strictly dependent on Gal alpha 1----4Gal beta-containing receptors, as shown by the absence of binding to cells from individuals of blood group P lacking these structures. Previous reports showed differences in the composition of globoseries glycolipids between erythrocytes from individuals of P1 and P2. No significant difference was found, However, in the mean adhesion to P1 and P2 epithelial cells or in the agglutination titer for P1 and P2 erythrocytes. The MR:GS receptors were equally distributed on squamous and transitional epithelial cells. In contrast, the distribution of MR:nonGS receptors was skewed. Attachment occurred mostly to squamous epithelial cells. The attachment of strains with MR:nonGS adhesins was independent of the P blood group of the cell donor. The binding ability of MR:GS and MR:nonGS adhesins appeared independent and additive. The attachment was not influenced by the ABH blood group. However, increased binding to epithelial cells from nonsecretors occurred regardless of the P blood group, suggesting a shielding of receptors by products controlled by the secretor genes. These results illustrate how individual variation in cell surface components with and without receptor activity determine the interaction of a ligand with a known receptor.

Adhesins, Escherichia coli↗

Virulence-associated traits in Escherichia coli causing first and recurrent episodes of urinary tract infection in children with or without vesicoureteral reflux.

Virulence-associated properties of 606 urinary isolates from 174 children with urinary tract infections were related to severity of infection and factors increasing host susceptibility, e.g., vesicoureteral reflux (grade II or higher) and P1 blood group phenotype. A high proportion of strains of Escherichia coli causing first or recurrent episodes of acute pyelonephritis in children without reflux expressed the previously noted high frequency of certain O antigens, resistance to serum killing, hemolysin production, and adhesive capacity. A significantly lower frequency of these traits and a higher frequency of non-E. coli were seen among isolates from children with pyelonephritis and reflux, cystitis, and asymptomatic bacteriuria. Reflux was thus found to be a determinant of the level of infection and of the bacterial properties required to produce pyelonephritis. Efforts aimed at preventing or treating urinary tract infection by interfering with "virulent" bacteria may be of less value in patients with recurrent pyelonephritis and reflux, who are most likely to develop renal scars.

Adhesiveness↗

Correlation of P blood group, vesicoureteral reflux, and bacterial attachment in patients with recurrent pyelonephritis.

Bacterial attachment to urinary-tract epithelium is important in the pathogenesis of urinary-tract infection. Most pyelonephritogenic Escherichia coli bind specifically to epithelial-cell receptors, which are glycolipids of the globoseries and also antigens in the P blood-group system. Among 36 girls with recurrent pyelonephritis who did not have vesicoureteral reflux, we found that attaching bacteria were common and the P1 blood-group phenotype was present in 97 per cent, as compared with 75 per cent of 84 age-matched children without urinary-tract infection (P less than 0.01). In 32 girls with recurrent pyelonephritis who had reflux, attaching bacteria were rare, and the frequency of the P1 phenotype was not significantly higher than in controls (82 per cent, P greater than 0.05). In the group of patients with the P1 phenotype, 68 per cent of the urinary bacterial isolates from those without reflux, but only 25 per cent of isolates from those with reflux, bound to globotetraosylceramide, as determined by a receptor-coating technique (P less than 0.001). Our data suggest that, in the absence of reflux, the P1 blood group contributes to susceptibility to recurrent pyelonephritis due to bacteria that bind to the glycolipid receptors of the globoseries. In the presence of reflux, uroepithelial attachment does not seem to confer an advantage to bacteria that infect the kidney.

Adhesiveness↗

Chemical and clinical studies on the interaction of Escherichia coli with host glycolipid receptors in urinary tract infection.

The role of glycosphingolipids as host receptors, and fimbriae as bacterial ligands, for the adhesive and hemagglutinating reactions of uropathogenic E. coli was assessed. Glycolipids including globotetraosylceramide and globotriaosylceramide, which contain the disaccharide Gal alpha 1 leads to 4Gal were bound by many strains isolated from patients with pyelonephritis and cystitis. The fimbriae of one strain were shown to serve as ligands for these receptors. Although most pyelonephritic E. coli recognized globotetraosylceramide, as measured by the agglutination of glycolipid coated erythrocytes, some also recognized D-mannose residues (i.e. mannose-sensitive hemagglutination). Several strains were exclusively mannose-sensitive or bound neither globotetraosylceramide nor mannose. A genetic basis for susceptibility to infection was indicated. The erythrocytes of blood group P2 have lower amounts of Gal alpha 1 leads to 4Gal containing glycolipids than individuals of blood group P1. Blood group P2 was significantly less frequent (1/28) among patients with recurrent urinary tract infection compared to the normal population (10/40, p less than 0.02). Therefore, globoseries glycolipids may be determinants of susceptibility to urinary tract infection.

Binding Sites↗

Different binding specificities of P. mirabilis compared to E. coli.

The target cell specificities of P. mirabilis and E. coli strains were compared using human urinary tract epithelial cells and erythrocytes from human, guinea pig, sheep, ox and horse blood. P. mirabilis strains agglutinated the erythrocytes both in mannose-resistant and mannose-sensitive patterns. No relation was, however, found between hemagglutination and adhesion to uroepithelial cells. This is in contrast to E. coli where uroepithelial cell attachment is paralleled by mannose-resistant agglutination o human erythrocytes. The difference in receptor recognition between P, mirabilis and E. coli was further indicated by the fact that P. mirabilis strains attaching to human uroepithelial cells did not agglutinate guinea pig red cells coated with globotetraosylceramide, acting as a receptor for E. coli on human uroepithelial cells erythrocytes.

Animals↗

Attachment of Proteus mirabilis to human urinary sediment epithelial cells in vitro is different from that of Escherichia coli.

The in vitro attachment of 335 Proteus mirabilis strains from various human sources to human urinary tract epithelial cells was measured. No significant difference in adhesive capacity was found between P. mirabilis strains isolated from the blood of 89 patients with bacteremia, the stools of 36 healthy subjects and 56 patients with diarrhea, and the urine of 62 adults and 92 children with bacteriuria. High mean adhesion values were observed in all groups. The P. mirabilis strains attached only to squamous cells and not to transitional epithelial cells, whereas most of the Escherichia coli strains tested attached to both cell types; strains from patients with acute pyelonephritis attached more often than those from patients with acute cystitis or asymptomatic bacteriuria. The attachment of P. mirabilis to squamous epithelial cells was high about day 15 of the menstrual cycle of the epithelial cell donor, but low at the beginning and the end of the cycle. In contrast, the attachment of E. coli to squamous and transitional epithelial cells did not vary significantly with the menstrual cycle of the cell donor. Differences in adhesion characteristics of E. coli and P. mirabilis may relate to the differences in clinical appearance of urinary tract infections produced by the two organisms.

Epithelial Cells↗

Recent progress in the understanding of the role of bacterial adhesion in the pathogenesis of urinary tract infection.

There is extensive evidence indicating that the capacity of Escherichia coli to attach to the mucosal lining of the urinary tract is a virulence factor in acute pyelonephritis in the unobstructed state. In vitro results using human uroepithelial cells and clinical E. coli isolates as well as in vivo work on ascending urinary tract infection in mice and E. coli strains with genetically defined adhesins support this notion. The biochemical characterization of the bacterial ligands and epithelial cell receptors important for the attachment of most pyelonephritogenic E. coli provides a more sophisticated means of evaluating the role of bacterial adhesion in urinary tract infection: 1) It allows precise diagnosis of the receptor specificity of clinical isolates; 2) The receptor can be used to isolate the relevant bacterial adhesins; 3) The localization and quantity of the receptor in the patient may be of prognostic importance; 4) The administration of soluble receptor analogues or antibodies to the adhesins may be useful for prophylactic and/or therapeutic purposes.

Adhesins, Escherichia coli↗