Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0034186 (pyelonephritis)
 6,144 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Uropathogenic Escherichia coli is the leading cause of urinary tract infection and hospital visits in North America. Cystitis and acute pyelonephritis, infection of the bladder and kidney, respectively, are the two most common syndromes encountered in patients with urinary tract infection. We sequenced and annotated 71,684 bases of a previously unidentified pathogenicity-associated island (PAI) from E. coli strain CFT073. This PAI contained 89 open-reading frames encoding a pap operon, iron-regulated genes, mobile genetic elements, and a large proportion of unknown or unidentified open-reading frames. Dot blot analysis with 11 DNA sequences from this PAI demonstrated that 7 sequences were more prevalent among uropathogens: 2 probes were more prevalent among cystitis and pyelonephritis isolates, 2 among pyelonephritis isolates only, and 3 among cystitis isolates only than among fecal isolates. These data suggest that groups of uropathogens have genetic differences that may be responsible for the different clinical outcomes.
 ...
PMID:Identification of DNA sequences from a second pathogenicity island of uropathogenic Escherichia coli CFT073: probes specific for uropathogenic populations. 1157 20

Recent work has demonstrated that expression of type 1 fimbriae is repressed by PapB, a regulator of pyelonephritis-associated pili (P-pili). PapB belongs to family of related adhesin regulators, for which consensus residues required for DNA binding and oligomerization have been identified. Of the regulators tested in this study, PapB, SfaB (S-fimbriae) and PefB (Salmonella enterica serovar Typhimurium--plasmid-encoded fimbriae) repressed FimB-promoted off-to-on inversion of the fim switch, although complete repression was only demonstrated by PapB. DaaA, FaeB, FanA, FanB and ClpB had no effect on fim switching. In addition, only PapB stimulated FimE-promoted on-to-off inversion. Deletion analysis demonstrated that this specificity resides in the carboxy terminal of the protein, and not the amino terminal, with the central region being homologous among the family members. Exchange of Leu(82) and Ile(83) of PapB for the equivalent residues from the DaaA protein (Phe and Gln) within the carboxy terminal virtually abolished cross-talk activity. Whereas PapB can bind to a region around the left inverted repeat of the fim switch, DaaA and the PapB double mutant were effectively unable to bind this region. A previously characterized PapB DNA binding mutant also failed to bind to this region and failed to inhibit FimB activity at the fim switch. Thus, repression of fim expression appears unique to PapB and SfaB within E. coli and requires DNA binding involving amino acid residues located both within the homologous core and in the heterogeneous carboxy terminus. The variation in the carboxy terminus between the PapB family members explains their differential effects on fim. This mechanism of cross-talk seems restricted to the P and S family adhesins with type 1 fimbriae and may ensure variable and sequential expression of adhesins during urinary tract infections.
 ...
PMID:PapB paralogues and their effect on the phase variation of type 1 fimbriae in Escherichia coli. 1170 57

Bacteria have developed an epigenetic phase variation mechanism to control cell surface pili-adhesin complexes between heritable expression (phase ON) and nonexpression (phase OFF) states. In the pyelonephritis-associated pili (pap) system, global regulators [catabolite gene activator protein (CAP), leucine-responsive regulatory protein (Lrp), DNA adenine methylase (Dam)] and local regulators (PapI and PapB) control phase switching. Lrp binds cooperatively to three pap DNA binding sites, sites 1-3, proximal to the papBA pilin promoter in phase OFF cells, whereas Lrp is bound to sites 4-6 distal to papBA in phase ON cells. Two Dam methylation targets, GATC(prox) and GATC(dist), are located in Lrp binding sites 2 and 5, respectively. In phase OFF cells, binding of Lrp at sites 1-3 inhibits methylation of GATC(prox), forming the phase OFF DNA methylation pattern (GATC(dist) methylated, GATC(prox) nonmethylated). Binding of Lrp at sites 1-3 blocks pap pili transcription and reduces the affinity of Lrp for sites 4-6. Together with methylation of GATC(dist), which inhibits Lrp binding at sites 4-6, the phase OFF state is maintained. We hypothesize that transition to the phase ON state requires DNA replication to dissociate Lrp and generate a hemimethyated GATC(dist) site. PapI and methylation of GATC(prox) act together to increase the affinity of Lrp for sites 4-6. Binding of Lrp at the distal sites protects GATC(dist) from methylation, forming the phase ON methylation pattern (GATC(dist) nonmethyated, GATC(prox) methylated). Lrp binding at sites 4-6 together with cAMP-CAP binding 215.5 bp upstream of the papBA transcription start, is required for activation of pilin transcription. The first gene product of the papBA transcript, PapB, helps maintain the switch in the ON state by activating papI transcription, which in turn maintains Lrp binding at sites 4-6.
 ...
PMID:Self-perpetuating epigenetic pili switches in bacteria. 1220 45

The expression of pyelonephritis-associated pili (Pap) in uropathogenic Escherichia coli is epigenetically controlled by a reversible OFF to ON switch. In phase OFF cells, the global regulator Lrp is bound to pap sites proximal to the pilin promoter, whereas in phase ON cells, Lrp is bound to promoter distal sites. We have found that the local regulator PapI increases the affinity of Lrp for the sequence "ACGATC," which contains the target "GATC" site for DNA adenine methylase (Dam) and is present in both promoter proximal and distal sites. Mutational analyses show that methylation of the promoter proximal GATC(prox) site by Dam is required for transition to the phase ON state by specifically blocking PapI-dependent binding of Lrp to promoter proximal sites. Furthermore, our data support the hypothesis that PapI-dependent binding of Lrp to a hemimethylated GATC(dist) site generated by DNA replication is a critical component of the switch mechanism.
 ...
PMID:The mechanism by which DNA adenine methylase and PapI activate the pap epigenetic switch. 1458 Mar 45

Proteus mirabilis compromises the care of many patients undergoing long-term indwelling bladder catheterization. It forms crystalline bacterial biofilms in catheters which block the flow of urine, causing either incontinence due to leakage or painful distention of the bladder due to urinary retention. If it is not dealt with, catheter blockage can lead to pyelonephritis and septicemia. We have examined the epidemiology of catheter-associated P. mirabilis infections by use of pulsed-field gel electrophoresis (PFGE) of NotI restriction enzyme digests of bacterial DNA. This technique was shown to be more discriminatory than the classical phenotypic Dienes typing technique. We demonstrated that each of 42 isolates from diverse environmental sources and 10 of 12 isolates from blood, wound swabs, and mid-stream urine samples of hospitalized patients had distinct genotypes. Examination of a set of 55 isolates of P. mirabilis, each from a different clinical or environmental source, identified 49 distinct genotypes and 43 Dienes types. The index of discrimination was 0.993 for the PFGE method and 0.988 for the Dienes method. Applying the PFGE method to isolates from catheter-associated urinary tract infections confirmed that the strains present in the crystalline catheter biofilms were identical to those isolated from the same patient's urine. An analysis of samples taken during a prospective study of infections in catheterized nursing home patients revealed that a single genotype of P. mirabilis can persist in the urinary tract despite many changes of catheter, periods of noncatheterization, and antibiotic therapy.
 ...
PMID:Molecular epidemiology of Proteus mirabilis infections of the catheterized urinary tract. 1460 24

To identify novel virulence-associated genes in uropathogenic Escherichia coli (UPEC) strains, a suppression subtractive hybridization strategy was applied to genomic DNA of four clinical UPEC isolates from patients suffering from cystitis or pyelonephritis. The genomic DNA of four isolates (tester strains) was subtracted from the DNA of two different driver strains, the well characterized UPEC strain CFT073 and the non-pathogenic E. coli K-12 strain MG1655. We determined the sequence of 172 tester strain-specific DNA fragments, 86 of which revealed only low or no homology to nucleotide sequences of public databases. We further determined the virulence association of the 86 novel DNA fragments using each DNA fragment as a probe in Southern hybridizations of a reference strain collection consisting of 60 extraintestinal pathogenic E. coli isolates, and 40 non-virulent E. coli strains from stool samples. From this, 19 novel DNA fragments were demonstrated to be significantly associated with virulent strains and thus may represent new virulence traits. Our results support the idea of a considerable genetic variability among UPEC strains and suggest that novel genomic determinants might contribute to virulence of UPEC.
 ...
PMID:Identification of novel virulence-associated loci in uropathogenic Escherichia coli by suppression subtractive hybridization. 1475 41

The possibility of a colonization and later urinary infection is due to a first contact among a series of structures of the bacterium, denominated adhesins (fimbrica or no-fimbrica) and some receivers or ligands of the surface of the urinary epitelium. The bacterial fimbriae of Escherichia coli, of those that have been studied up to seven different types, are protean structures coded by the chromosomal DNA, being the most important those of type 1, in connection with the colonization of the low roads, and the type P, with the cystitis and pyelonephritis. They are studied with detail their different protean components and the very complex genetic regulation of their production, made of great interest in the pathogeny of these infections and in the possibility of their prevention. The receivers of each fimbriae type are also chemically different, and their knowledge would explain important clinical data.
 ...
PMID:[Bacterial adherence in pathogenesis of urinary tract infectious]. 1502 98

Toll-like receptors (TLR) are an emerging family of receptors that recognize pathogen-associated molecular patterns and promote the activation of leukocytes and intrinsic renal cells. Ligands of the TLR include exogenous microbial components such as LPS (TLR4), lipoproteins and peptidoglycans (TLR1, -2, -6), viral RNA (TLR3), bacterial and viral unmethylated cytosin-guanosin dinucleotide (CpG)-DNA (TLR9), and endogenous molecules including heat-shock proteins and extracellular matrix molecules. Upon stimulation, TLR induce expression of inflammatory cytokines or costimulatory molecules via the MyD88-dependent and MyD88-independent signaling pathways shared with the interleukin-1 receptors. TLR are differentially expressed on leukocyte subsets and non-immune cells and appear to regulate important aspects of innate and adaptive immune responses. Tubular epithelial cells are among the non-immune cells that express TLR1, -2, -3, -4, and -6, suggesting that these TLR might contribute to the activation of immune responses in tubulointerstitial injury (e.g., bacterial pyelonephritis, sepsis, and transplant nephropathy). In addition, TLR9 has been shown to be involved in antigen-induced immune complex glomerulonephritis and lupus nephritis by regulating humoral and cellular immune responses. TLR are evolutionary conserved regulators of innate and adaptive immune responses. It is likely that TLR are involved in many if not all types of renal inflammation. Here the authors provide an overview on the biology of TLR, summarize the present data on their expression in the kidney, and provide an outlook for the potential roles of TLR in kidney disease.
 ...
PMID:Signaling danger: toll-like receptors and their potential roles in kidney disease. 1503 87

Bacteria have developed epigenetic mechanisms to control the reversible Off-to-On switching of cell surface structures such as pyelonephritis-associated pili (PAP). The pap pili switch is primarily controlled by the global regulator leucine-responsive regulatory protein (Lrp), the local regulator PapI, and DNA adenine methylase (Dam). There are two sets of binding sites for Lrp in the pap regulatory region: promoter proximal sites 1,2,3 and promoter distal sites 4,5,6. The pilin promoter proximal (GATCprox) and distal (GATCdist) targets for Dam are located within Lrp binding sites 2 and 5, respectively. In the Off state, Lrp binds cooperatively to sites 1,2,3 overlapping the papBA pilin promoter, shutting off pilin transcription, and blocking methylation of GATCprox. Binding of Lrp at sites 1,2,3, together with methylation of GATCdist, reduces the affinity of Lrp for sites 4,5,6, preventing simultaneous binding of Lrp at sites 4,5,6 upstream. Switching to the phase. On state requires the environmentally regulated PapI co-regulator, which increases the affinity of Lrp for sites 5 and 2. PapI binds specifically to Lrp-pap DNA complexes via binding with Lrp as well as contact with DNA sequences within pap sites 5 and 2. Directionality in switching from Off to On appears to be due to methylation of GATCprox, which prevents formation of the PapI-Lrp-pap site 2 ternary complex. A switch model is presented in which DNA replication is proposed to play a critical role by generating a hemimethylated GATCdist site and displacing Lrp from sites 1,2,3. This facilitates methylation of GATCprox and binding of PapI-Lrp to sites 4,5,6, with subsequent activation of pap transcription. The first gene product of the pap operon, PapB, positively regulates papI transcription, resulting in a positive feedback loop that helps maintain the On state. The pap switch is environmentally regulated by a number of factors including the CpxAR two-component regulatory system, the Histone-like nucleoid structuring protein H-NS, and cAMP-Catabolite Gene Activator Protein (CAP), which all involve binding of regulatory binding proteins to pap DNA sequences with subsequent alteration of PapI and Lrp binding. The Pap switch mechanism, with interesting variations, is conserved among a number of enteric bacteria, controlling expression of many unrelated pili-adhesin complexes.
 ...
PMID:The intricate workings of a bacterial epigenetic switch. 1523 94

In the process of examination of 156 children of different age groups 176 E. coli cultures were isolated; of these, 98 cultures were isolated from acute cystitis and pyelonephritis patients, 28--from urine in cases of aysmptomatic bacteriuria, 30--from feces in cases of asymtomatc bacteriuria and intestinal dysbacteriosis, while 20 cultures--from feces of healthy children. In these bacteria the presence of genes associated with pathogenicity islets (PI) hlyA, hlyB, cnf-1, papC, sfaG and gene irp-2 (iron-regulated protein) was established with PCR. The detection rate of PI determinants in uropathogenic E. coli (UPEC) was shown to depend on the variants of the clinical manifestation of urinary tract infection. The total detection rate of PI gene fragments in UPEC cultures of different origin was indicative of their definitely less frequent occurrence in asymptomatic bacteriuria, observed simultaneously with intestinal dysbacteriosis, in comparison with acute urological infection. Practically the same detection rate of PI determinants in E. coli, isolated in asymptomatic bacteriuria in children, reflected high probability of genetic exchange in the above-mentioned fragments and made it possible to presume the existence of DNA sites, characteristic mainly of pathogenic clones. The established heterogeneity of the detection rate of PI determinants in E. coli clinical isolates requires further study.
 ...
PMID:[Genetic determinants of Escherichia coli pathogenicity isolated from urine and feces of children with different clinical variants of urinary system infection]. 1548 10


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>