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Query: UMLS:C0034186 (pyelonephritis)
 6,144 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of this study was to assess the possible relationship between secretor state and the inflammatory response to urinary tract infection (UTI). Girls with recurrent UTI were prospectively studied. They included 61 secretor and 23 non-secretor individuals with 604 episodes of recurrent UTI. The response to each UTI episode was measured as the levels of C-reactive protein, erythrocyte sedimentation rate and the body temperature as well as renal concentrating capacity and pyuria. The levels of C-reactive protein, erythrocyte sedimentation rate and the body temperature were significantly higher in non-secretors than in secretors (p less than 0.04). As a consequence, non-secretors had an increased probability of being assigned a diagnosis of acute pyelonephritis rather than asymptomatic bacteriuria (p less than 0.05). The higher inflammatory response in non-secretors was independent of the Gal alpha 1-4Gal beta adhesin expression of the infecting Escherichia coli strains. The increased inflammatory response to UTI in non-secretors might explain the accumulation of these individuals among patients with renal scarring.
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PMID:Blood group non-secretors have an increased inflammatory response to urinary tract infection. 158 29

Digalactoside-binding (Gal-Gal) pili and alpha-hemolysin of Escherichia coli have been implicated as important virulence determinants in the pathogenesis of human ascending, nonobstructive pyelonephritis. The pathogenic significance of these determinants was evaluated in vitro and in the BALB/c mouse pyelonephritis model by employing wild-type, avirulent laboratory, and genetically defined cosmids, transformants, and recombinant strains. In vitro data suggest that the cytolytic activity of hemolysin is significantly (P less than 0.05) enhanced among digalactoside-binding strains which agglutinate erythrocytes. The basis of increased hemolysis is related presumably to more efficient delivery of the toxin to target lipid substrate in the host plasma membrane. Intravesicular administration of bacteria that express both digalactoside binding and hemolysin generally resulted in greater mortality and renal parenchymal injury in mice than strains that expressed none or only one of these determinants. Analyses convincingly demonstrate that digalactoside-binding pili are correlated with upper urinary tract colonization and that hemolysin is correlated with septicemia and renal parenchymal damage. These determinants collectively constitute the minimal virulence factors to produce disease in this model. Their efficacy as vaccines for the prevention of pyelonephritis was also assessed. A purified Gal-Gal pilus vaccine prevented (P less than 0.05) subsequent colonization by a challenge wild-type strain that exhibited homologous pili. The hemolysin vaccine did not abrogate subsequent bacterial renal colonization on challenge, but it did protect (P less than 0.05) mice which survived challenge from subsequent renal injury compared with those in the saline control group. The combination of these determinants was also protective. The combination of Gal-Gal pili and hemolysin in a vaccine preparation represents a potentially worthwhile strategy for human immunoprophylaxis against pyelonephritis by interdicting several steps in the pathogenesis of a bacterial mucosal infection.
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PMID:Alpha-hemolysin contributes to the pathogenicity of piliated digalactoside-binding Escherichia coli in the kidney: efficacy of an alpha-hemolysin vaccine in preventing renal injury in the BALB/c mouse model of pyelonephritis. 167 76

The frequency of Escherichia coli with Gal alpha 1-4Gal beta-specific adhesins is reduced among children who develop renal scars. The adhesion-negative phenotype may be due to the absence of the pap DNA sequences which encode these adhesins or to a phase variation event induced by in vitro culture. In the present study the frequency of pap and pil homologous DNA was determined by dot blot analysis with probes specific for the respective sequence using E. coli strains from children with recurrent pyelonephritis with and without renal scarring. The frequency of pap was 79% in the strains isolated from the nonscarring group compared with 39% in the strains from the scarring group (P less than 0.001). The Gal alpha 1-4Gal beta phenotype was expressed by 89% of the pap-positive strains from the nonscarring group compared with 71% in the scarring group (P less than 0.05). In addition 13 of 77 of the pap-positive E. coli strains agglutinated sheep erythrocytes but not the Gal alpha 1-4Gal beta latex beads; a reaction attributed to reactivity with the Forssman glycolipid. DNA sequences homologous with pil were found in 95% of all strains and there was no significant difference between the nonscarring and the scarring groups. The low frequency of Gal alpha 1-4Gal beta specific strains in the scarring group was therefore due to the absence of pap-homologous DNA sequences and to a reduced rate of phenotypic expression among pap-positive scarring strains. There was no support for a relationship between type 1 fimbriae and renal scarring.
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PMID:Escherichia coli in patients with renal scarring: genotype and phenotype of Gal alpha 1-4Gal beta-, Forssman- and mannose-specific adhesins. 167 31

Pyelonephritis-associated pili (Pap) are important in the pathogenesis of ascending, unobstructive Escherichia coli-caused renal infections because these surface bacterial organelles mediate digalactoside-specific binding to host uroepithelial cells. Pap are composed of many different polypeptides, of which only the tip proteins mediate specific binding. The PapA moiety polymerizes to form the bulk of the pilus structure and has been employed in vaccines despite its lack of Gal alpha(1-4)Gal receptor specificity. Animal recipients of PapA pilus-based vaccines are protected against experimental pyelonephritis caused by homologous and heterologous Gal-Gal-binding uropathogenic E. coli strains. Specific PapA immunoglobulin G antibodies in urine are correlated with protection in these infection models. The nucleotide sequences of the gene encoding PapA were determined for three E. coli clones expressing F7(1), F7(2), and F9 pili and were compared with corresponding sequences for other F serotypes. Specific rabbit antisera were employed in enzyme-linked immunosorbent assays to study the cross-reactivity between Gal-Gal pili purified from recombinant strains expressing F7(1), F7(2), F9, or F13 pili and among 60 Gal-Gal-binding wild-type strains. We present data which corroborate the concept that papA genes are highly homologous and encode proteins which exhibit greater than 70% homology among pili of different serotypes. The differences primarily occur in the cysteine-cysteine loop and variable regions and constitute the basis for serological diversity of these pili. Although there are differences in primary structures among these pili, antisera raised against pili of one serotype cross-reacted frequently with many other Gal-Gal pili of different serotypes. Furthermore, antisera raised against pili of the F13 serotype cross-reacted strongly or moderately with 52 (86%) of 60 wild-type Gal-Gal-binding E. coli strains. These data suggest that there are common immunogenic domains among these proteins. These additional data further support the hypothesis that broadly cross-protective PapA pilus vaccines for the immunoprophylaxis of pyelonephritis might be developed.
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PMID:DNA sequences of three papA genes from uropathogenic Escherichia coli strains: evidence of structural and serological conservation. 168 51

Most urinary tract infections (UTI) are caused by Escherichia coli (E. coli) and the pathogenetic mechanisms of this bacterium have been thoroughly studied. Lipopolysaccharide (LPS), capsular polysaccharides and fimbrial structures are among the more important virulence markers. P-fimbriae, with a specificity for the carbohydrate structure of the P blood group system (alpha-D-Gal-1,4-beta-D-Gal) have attracted particular interest, as non-fimbriated E. coli rarely give rise to pyelonephritis, unless the normal defence mechanisms of the urinary tract are impaired. We have evaluated a commercial test (Orion Diagnostica, PF test), developed to detect P-fimbriae on E. coli from clinical isolates. It is based on latex particles with covalently bound receptors (alpha-D-Gal-1,4-beta-D-gal). In this study a high correlation was found between pyelonephritis, as judged by clinical and biochemical criteria, and a positive PF test.
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PMID:A simple reliable agglutination test for screening P-fimbriated Escherichia coli in children with urinary tract infections gives valuable clinical information. 135 34

E. coli cause greater than 90% of urinary tract infections (UTI) in childhood. The capacity to adhere to urinary tract epithelial cells characterizes E. coli strains that cause acute pyelonephritis. Galactose alpha 1-4Galactose beta is the minimal receptor for adhering uropathogenic E. coli. Gal alpha 1-4Gal beta-binding bacteria caused significantly higher body temperature, C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), pyuria, and lower renal concentrating capacity than E. coli lacking this specificity. The binding bacteria thus appeared to be more potent inducers of acute inflammation. Since inflammation may lead to tissue damage, we examined the relationship of infection with Gal alpha 1-4Gal beta-positive bacteria to renal scarring. The frequency of renal scarring was 5% in boys with Gal alpha 1-4Gal beta-positive and 40% in boys with Gal alpha 1-4Gal beta-negative E. coli. Analysis of binding capacity with the help of a newly developed latex agglutination assay can thus be used as an effective predictor of risk for renal scarring.
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PMID:Bacterial attachment, inflammation and renal scarring in urinary tract infection. 181 92

Escherichia coli (E. coli) causes greater than 90% of urinary tract infections, UTI, in childhood. The capacity to adhere to urinary tract epithelial cells characterizes E. coli strains that cause acute pyelonephritis. Adherence of uropathogenic E. coli is the result of a specific interaction between bacterial adhesins and glycolipid receptors on the host cells, especially the globoseries of glycolipids which share the Galactose alpha 1-greater than 4Galactose beta disaccharide (Gal alpha 1-greater than 4Gal beta). In childhood UTI, Gal alpha 1-greater than 4Gal beta-binding bacteria caused significantly higher body temperature, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and pyuria, and lower renal concentrating capacity, than E. coli lacking this specificity. The Gal alpha 1-greater than 4Gal beta-binding bacteria thus appeared to be more potent inducers of inflammation than other strains. Since inflammation may lead to tissue damage we examined the relationship of infection with Gal alpha 1-greater than 4Gal beta-positive bacteria to renal scarring. The frequency of renal scarring was 5% in boys with Gal alpha 1-greater than 4Gal beta-positive and 40% in boys with Gal alpha 1-greater than 4Gal beta-negative E. coli. Bacterial binding to Gal alpha 1-greater than 4Gal beta can be detected with a commercially available test reagent. This reagent can thus be used as an effective predictor of risk for renal scarring. Interleukin-6 (IL-6) is a pyrogen and inducer of the acute phase reactants. It was shown to be produced locally in the urinary tract, in response to UTI, and to spread systemically. Mucosal challenge with dead bacteria was sufficient to induce the IL-6 response. Circulating IL-6, and/or IL-1 and tumor necrosis factor could explain the fever, as well as increased ESR and CRP found in association with acute symptomatic UTI.
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PMID:Bacterial adherence as a virulence factor in urinary tract infection. 228 1

Synthetic peptides corresponding to five segments of a globoside (Gal-Gal)-binding pilin sequence [residues 5-12 (R5-12), R65-75, R93-104, R103-116, and R131-143], cyanogen bromide fragment II (CNBr-II, R53-163), and purified, intact Gal-Gal pili were prepared as vaccines and tested for their efficacy in a BALB/c murine model of pyelonephritis. Intact Gal-Gal pili, CNBr-II, and synthetic peptides R5-12 and R65-75 engendered antibodies that bound the homologous pilin protein and prevented urine and renal colonization in most vaccine recipients. Protection correlated with serum anti-pilus IgG ELISA titers greater than or equal to 1:250. The efficacy afforded by synthetic peptides R5-12 and R65-75 in vaccinated mice indicates that linear "antigenic" determinants in separate cyanogen bromide fragments encode "protective" epitopes. Peptides R93-104, R103-116, and R131-143 lacked efficacy, indicating that not all regions of the sequence are serologically equivalent. The crossreactivity of the peptide antisera for different Gal-Gal pilins was also assessed and correlated with the sequence homology of the corresponding regions. Antiserum to peptide R65-75, which corresponds to a region of unconserved sequence in heterologous pilins, bound only the homologous pilin. Thus, it specifies a type-specific protective epitope. Antiserum to synthetic peptide R5-12, which corresponds to a region of conserved sequence, bound Gal-Gal pilins from seven of eight pyelonephritis strains, indicating that it specifies a crossreacting protective epitope.
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PMID:Synthetic peptides corresponding to protective epitopes of Escherichia coli digalactoside-binding pilin prevent infection in a murine pyelonephritis model. 244 96

The initial pathogenic step in nonobstructive Escherichia coli pyelonephritis usually involves the binding of a bacterial adhesin with host uroepithelial glycoprotein receptors containing the D-Gal p alpha 1----4 D-Gal p beta 1 (Gal-Gal) moiety. In this study, groups of mice were immunized with Gal-Gal pili and challenged 2 wk later intravesicularly with E. coli strains expressing homologous or heterologous pili. 63 of 129 pili-immunized mice (49%) were protected from subsequent E. coli renal colonization compared with 5 of 85 control mice (6%). Among mice that had E. coli cultured from their right kidney, control mice had greater bacterial colony counts than pili-immunized animals (P less than 0.05). Light microscopic examination of kidneys demonstrated less histopathology among pili immunized mice than among control mice (P less than 0.05). Protection correlated with the presence of specific IgG antibodies in the urine and serum that bind to the major pilin structural polypeptide and not to the Gal-Gal pili tip adhesin per se. These results support the concept that immunization with a bacterial surface-coat constituent can prevent mucosal infection by interfering with colonization. Also Gal-Gal pili of E. coli represent a suitable candidate for immunoprophylaxis against pyelonephritis.
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PMID:Gal-Gal pili vaccines prevent pyelonephritis by piliated Escherichia coli in a murine model. Single-component Gal-Gal pili vaccines prevent pyelonephritis by homologous and heterologous piliated E. coli strains. 256 25

The linear immunogenic and antigenic structure of E. coli Gal-Gal pili from the recombinant strain HU 849 was investigated with nine synthetic peptides corresponding to regions of the pilus sequence predicted to contain hydrophilic beta-turns. Five peptides, as bovine serum albumin conjugates, were found by anti-HU 849 pilus serum and were thus designated "immunogenic epitopes." Peptides corresponding to R 25-38, R 38-50, and R 48-61 (which jointly comprise the single intramolecular disulfide loop), and R 103-116, were bound in low titer. A prominent immunogenic epitope was specified by a peptide corresponding to R 65-75. Four peptides, as thyroglobulin conjugates, elicited antisera in rabbits that bound intact HU 849 pili. These were designated "antigenic epitopes." Two prominent antigenic epitopes were localized to peptides corresponding to R 5-12 and R 93-104, whereas peptides corresponding to R 65-75 and R 119-131 represented two minor antigenic epitopes. None of the peptide antisera bound Gal-Gal pili from heterologous strains except anti-R 93-104 and anti-R 5-12. In 8 of the 10 Gal-Gal-binding pyelonephritis isolates tested, anti-R 5-12 detected a protein with an apparent molecular weight of 18,000 co-migrating with several Gal-Gal pili. Anti-R 93-104 detected a corresponding protein in 4 of 8 fecal and 7 of 12 pyelonephritis Gal-Gal-binding isolates; however, it also bound apparently unrelated proteins of higher molecular weight.
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PMID:Gal-Gal pyelonephritis Escherichia coli pili linear immunogenic and antigenic epitopes. 258 37


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