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Synthetic peptides corresponding to protective epitopes of Escherichia coli digalactoside-binding pilin prevent infection in a murine pyelonephritis model.

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.

Animals↗

The Gal(alpha 1-4)Gal-specific tip adhesin of Escherichia coli P-fimbriae is needed for pyelonephritis to occur in the normal urinary tract.

Nonobstructive acute pyelonephritis in humans is most often caused by P-fimbriated Escherichia coli. P-fimbriae are heteropolymeric fibers carrying a Gal(alpha 1-4)Gal-specific PapG adhesin at its distal end. The pyelonephritic strain DS17 expresses P-fimbriae from a single gene cluster. A mutant strain, DS17-8, which expresses P-fimbriae tacking the PapG adhesin, was constructed by allelic replacement introducing a 1-bp deletion early in the papG gene. In cynomolgus monkeys, DS17 and DS17-8 were equally able to cause bladder infection, whereas only the wild-type strain DS17 could cause pyelonephritis as monitored by bacteriological, functional, and histopathological criteria. Since DS17, but not DS17-8, adheres to renal tissue, these data underscore the critical role of microbial adherence to host tissues in infectious disease and strongly suggest that the PapG tip adhesin of P-fimbriae is essential in the pathogenesis of human kidney infection.

Adhesins, Escherichia coli↗

Acute pyelonephritis caused by Mycoplasma hominis.

A 59-yr-old male alcoholic with bilateral nephrocalcinosis and upper urinary tract stones presented with fever, acute abdominal signs and ascites. Laparotomy revealed the presence of 1.5 litres of ascitic fluid and confirmed right-sided acute pyelonephritis. Culture of urine from the renal pelvis obtained during surgery was positive for Mycoplasma hominis. Initial therapy with cefuroxime failed and doxycycline was later initiated when culture was positive for Mycoplasma hominis, with definite clinical improvement. This is an unusual case of acute pyelonephritis with peritoneal signs and ascites due to Mycoplasma hominis in an elderly male who had no recent history of urinary tract instrumentation.

Alcoholism↗

Fewer bacterial relapses after oral treatment with norfloxacin than with ceftibuten in acute pyelonephritis initially treated with intravenous cefuroxime.

This double-blind, multicentre study was performed at nine centres on a total of 171 patients who presented with fever (> 38.5 degrees C) and signs of acute pyelonephritis. All were initially treated with intravenous cefuroxime. After 2-3 d, when the fever had subsided and urinary culture had revealed growth of Gram-negative bacteria ( > 10(7) colony-forming units per litre), treatment was changed to oral administration of ceftibuten 200 mg b.i.d. or norfloxacin 400 mg b.i.d. for 10 d. The patients were followed for signs of bacterial or clinical relapse 7-14 d after the end of treatment. The initial clinical and bacteriological cure was excellent in both groups, but there were significantly fewer bacterial relapses after oral treatment with norfloxacin than with ceftibuten in acute febrile pyelonephritis initially treated with intravenous cefuroxime. The causal strain was eradicated in 75% of patients (73% of males, 76% of females) in the ceftibuten group and in 89% of patients (94% of males, 85% of females) in the norfloxacin group. The relative frequency of eradication was 0.84 (p < 0.05; 95%, confidence interval 0.74-0.97). Adverse events were reported by 47% of the patients in the ceftibuten group and by 38% in the norfloxacin group. This difference was not significant, but diarrhoea or loose stools occurred more frequently in the ceftibuten group.

Acute Disease↗

Double cancers of the kidney and ureter complicated with emphysematous pyelonephritis within the parenchyma of the renal tumour.

Emphysematous pyelonephritis and double cancers of the kidney and urinary tract are rare. We describe here a case of a diabetic man who had simultaneous renal cell carcinoma of the right kidney and transitional cell carcinoma of the right ureter complicated with emphysematous pyelonephritis within the tumour parenchyma of renal cell carcinoma. Imaging and pathology are demonstrated.

Aged↗

[Emphysematous pyelonephritis in a diabetic patient. Literature review apropos of a case].

We report the history of a 65-year-old woman, diabetic for 25 years who presented progressive alteration of consciousness with hyperthermia, right upper quadrant pain and vomiting. Bacteriological and radiographic investigations, especially computerized tomography scan of the abdomen, led to the diagnosis of emphysematous pyelonephritis caused by Escherichia coli. Despite a large spectrum antibiotic therapy and surgical drainage of the gas collection, the patient remained septic. An emergency nephrectomy was eventually performed. We review the characteristics of emphysematous pyelonephritis. Early diagnosis is essential because without early nephrectomy mortality rates reach 75%.

Aged↗

Unusual clinical presentation of Klebsiella pneumoniae induced endogenous endophthalmitis and xanthogranulomatous pyelonephritis in a non-nephrolithiasis and non-obstructive urinary tract.

The genitourinary tract is well recognized as a route through which bacteria could gain access to the blood circulation. Under some circumstances, metastatic infections may occur in distant organs, including endogenous endophthalmitis. Xanthogranulomatous pyelonephritis (XGP) is an unusual variant of chronic pyelonephritis. It most often occurs in middle-aged women who frequently have a history of recurrent urinary tract infections combined with obstruction and a kidney of poor function. We reported an unusual case of urinary tract infection in a non-nephrolithiasis and non-obstructive urinary tract complicated by Klebsiella pneumoniae endogenous endophthalmitis and developed XGP in two months.

Aged↗

Mycotic aneurysm presenting as acute pyelonephritis.

This report describes a 56-year-old man with a ruptured infected abdominal aortic aneurysm secondary to Salmonella bacteremia, initially presenting as acute pyelonephritis. Spike fever with severe back pain continued despite empiric antibiotic treatment at a local hospital. Hypotension with a sudden hemoglobin drop was observed on the second hospitalization day. Abdominal computed tomography to further examine the bleeding focus confirmed a rupture of the mycotic abdominal aortic aneurysm. This case was successfully treated through prompt surgical intervention and aggressive protracted antibiotic therapy. The case presented herein raises concerns about the uncommon but life-threatening mycotic aneurysm presented initially as acute pyelonephritis. Early diagnosis and appropriate surgical and antibiotic treatment of the Salmonella mycotic aortic aneurysm is crucial for a satisfactory outcome.

Acute Disease↗

Pyelitis, an important factor in the pathogenesis of retrograde pyelonephritis.

Pyelitis with acute and chronic pyelonephritis and also primary chronic pyelitis were easily initiated in female rats by a single non-traumatic retrograde infusion of bacteria into the urinary tract. The virulence of the bacterial species and the time of observation were related to the type and extent of lesions, but pyelitis regardless of the virulence appeared to be an important factor. The apex and fornix of the renal pelvic lumen were anatomic sites of persistent pyelitis which permitted local proliferation of bacteria for long periods. Cortical and medullary lesions were anatomically related to these areas of underlying pyelitis. Spread of infection followed a pattern of contiguity rather than ascending tubular infection. The experimental model has many of the features of chronic urinary infections in man and suggests that pyelitis is an important factor in the pathogenesis of chronic pyelonephritis initiated by retrograde infection.

Animals↗

Localization and fate of Escherichia coli in hematogenous pyelonephritis.

1. Hematogenous E. coli pyelonephritis was produced in rats. The localization of the organisms and the persistence of bacterial antigens was followed by fluorescent antibody techniques as well as by standard histological and bacteriological methods. 2. Salient sequential features were as follows: Single organisms passed through vessel walls into the renal interstitium and began multiplication and subsequently evoked a leucocytic response. Bacterial multiplication did not occur in glomeruli or renal tubular cells. Bacteria did not appear within renal tubular lumina until microabscesses were well developed in the renal interstitium. Bacteriuria appeared late and represented secondary invasion rather than filtration of organisms. The infection healed spontaneously but, while sterile, the parenchymal scars contained large amounts of residual bacterial antigen. The persistence of bacterial antigen did not result in continuing inflammatory changes or progressive scarring. 3. The persistence of bacterial antigens is postulated to constitute a major antigenic stimulus responsible for active immunity in experimental hematogenous pyelonephritis.

Animals↗

Retrograde Proteus pyelonephritis in rats. Localization of antigen and antibody in treated sterile pyelonephritic kidneys.

Rats with retrograde proteus pyelonephritis were treated with antibiotics until their kidneys became sterile. Using fluorescent antibody techniques, specific P. mirabilis antigen was found in some sterile pyelonephritic kidneys 20 weeks after cessation of treatment and presumed renal sterilization. Persistent antigen was associated with interstitial chronic inflammation but not with acute inflammation or progressive scarring. Rat gamma globulin and proteus antibody were localized in plasma cells of the renal inflammatory infiltrates. It is suggested that persistent antigen in chronic pyelonephritis may lead to the continued local appearance of antibody-producing cells.

Animals↗

Host-parasite interaction in the rat renal pelvis: a possible role for pili in the pathogenesis of pyelonephritis.

The initial interaction between bacteria and the renal pelvic epithelium may determine whether intrarenal infection occurs. A model of retrograde pyelonephritis was employed to study these events by electron microscopy. Female rats received an intravesicular inoculation of a 0.5-ml suspension of Proteus mirabilis containing 10(8) organisms. At intervals after inoculation, the kidneys were fixed by intravascular perfusion and the tissues were prepared for electron microscopy. During the first 24 h, increasing numbers of bacteria were seen to be attached by pili to the renal pelvic epithelial cells. The organism appeared to cross the mucosal barrier by several mechanisms: (a) penetration into the cytoplasm of intact epithelial cells, (b) passage between epithelial cells that were separated by excessive hydrostatic pressure generated during bladder inoculation, (c) passage across necrotic regions of the pelvis, and (d) translocation to the cortex by calicotubular backflow. Whereas at inoculation bacteria possessed pili 40 A in diameter (type III pili) 24 h after reflux, the predominant type of pili measured 70 A in thickness (type IV pili). Repetitive subculture induced a similar transition in vitro. To assess the influence of pili type on virulence in this model, 80 rats were challenged with either type III or type IV pilated organisms and the frequency of rats with cortical abscesses were compared at 1 wk. A significantly greater number of rats inoculated with type IV pilated Proteus manifested macroscopic evidence of infection. These results suggest that pili play a role in the pathogenesis of ascending pyelonephritis.

Animals↗

Gal-Gal pyelonephritis Escherichia coli pili linear immunogenic and antigenic epitopes.

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.

Amino Acid Sequence↗

Interleukin 8 receptor deficiency confers susceptibility to acute experimental pyelonephritis and may have a human counterpart.

Neutrophils migrate to infected mucosal sites that they protect against invading pathogens. Their interaction with the epithelial barrier is controlled by CXC chemokines and by their receptors. This study examined the change in susceptibility to urinary tract infection (UTI) after deletion of the murine interleukin 8 receptor homologue (mIL-8Rh). Experimental UTIs in control mice stimulated an epithelial chemokine response and increased chemokine receptor expression. Neutrophils migrated through the tissues to the epithelial barrier that they crossed into the lumen, and the mice developed pyuria. In mIL-8Rh knockout (KO) mice, the chemokine response was intact, but the epithelial cells failed to express IL-8R, and neutrophils accumulated in the tissues. The KO mice were unable to clear bacteria from kidneys and bladders and developed bacteremia and symptoms of systemic disease, but control mice were fully resistant to infection. The experimental UTI model demonstrated that IL-8R-dependent mechanisms control the urinary tract defense, and that neutrophils are essential host effector cells. Patients prone to acute pyelonephritis also showed low CXC chemokine receptor 1 expression compared with age-matched controls, suggesting that chemokine receptor expression may also influence the susceptibility to UTIs in humans. The results provide a first molecular clue to disease susceptibility of patients prone to acute pyelonephritis.

Animals↗

Local production of inflammatory mediators in an experimental model of acute obstructive pyelonephritis.

To investigate bacterial growth and inflammatory mediator release in the early stage of the immune response, a unilateral acute ascending pyelonephritis was induced in rats by intrabladder inoculation of Escherichia coli. The infected left kidney showed a significant bacterial proliferation, local production of interleukin (IL)-6 and IL-8 as detected by immunocytochemistry, and extensive destruction of renal parenchyma associated with impressive leukocyte recruitment. Inducible and constitutive nitric oxide synthases (NOS) were locally expressed, and a time-dependent increase in urinary secretion of nitric oxide (NO) was seen that could be blocked by NG-monomethyl-L-arginine. However, there was a discrepancy between the NO profile in the kidney and urine. The results demonstrate that in the early stage of acute pyelonephritis kidney tubules participate actively in the local host response by producing important inflammatory mediators and that urinary NO levels are not suitable for predicting renal NOS activity.

Acute Disease↗

Predominance of class II papG allele of Escherichia coli in pyelonephritis in infants with normal urinary tract anatomy.

P-fimbrial genotypes of Escherichia coli strains and their possible association with urinary tract abnormalities were studied in infants with pyelonephritis. A total of 153 urinary E. coli strains were analyzed by polymerase chain reaction for class I, II, and III alleles of the pyelonephritis-associated adhesin gene papG. Strains with any class II papG alleles were found significantly more often in infants with normal anatomy and function or in infants with clinically insignificant abnormalities than they were in infants with significant abnormalities (90 of 119 vs. 14 of 34 infants; P<. 001). On the other hand, strains without any papG alleles were found significantly more often in infants with major urinary tract abnormalities (11 of 34 vs. 17 of 119 infants; P=.016). Our genotypic findings indicate that, especially in infants with a normal urinary tract, infection is caused by more-virulent E. coli than is present in infants without a normal urinary tract. This virulence could be due to expression of pyelonephritogenic P fimbriae by an infecting E. coli strain.

Adhesins, Escherichia coli↗

Blood cultures for women with uncomplicated acute pyelonephritis: are they necessary?

To assess the utility of blood cultures in the management of uncomplicated pyelonephritis in women, we prospectively collected data from 583 cases. Discordant cases were defined as those for which the pathogens isolated from urine and from blood were different. We found that 97.6% of cases were nondiscordant. Clinical and microbiological evolution of infection did not differ between the 2 groups, and no changes of antibiotic therapy were required on the basis of blood culture results. Blood culture may not be routinely required for the evaluation of uncomplicated pyelonephritis in women.

Adult↗

A specific urinary cast in acute pyelonephritis.

A specific type of urinary cast has been demonstrated in the urine of patients who have acute pyelonephritis. This cast is characterized by the presence of bacteria in its matrix and appears to be specific for and diagnostic of pyelonephritis. It is easily demonstrated by routine urinalysis.

Antibody-Coated Bacteria Test, Urinary↗