P-fimbriae vaccines

Protection against acute pyelonephritis was induced by immunization of baboons with purified P-fimbriae ofEscherichia coli as vaccines. To test for cross-protective capacity of two different P-fimbriae vaccines we vaccinated baboons with P-fimbriae purified from eitherE. coli strain ER2 or strain JR1 and subsequently challenged the animals withE. coli strain JR1. All vaccinated animals showed elevated antibody titers to P-fimbriae from both of theE. coli strains used. Both vaccines tended to reduce the time of bacteriuria. They partially prevented pyelonephritis and protected against loss of renal function.     

LOSS OF FIMBRIAL ADHESION WITH THE ADDITION OF VACCINUM MACROCARPON TO THE GROWTH MEDIUM OF P-FIMBRIATED ESCHERCHIA COLI

Purpose

Vaccinium macrocarpon-the American cranberry-irreversibly inhibits the expression of P-fimbriae of E. coli. Further effects on the function and expression of P-fimbriae were studied by growing P-fimbriated E. coli in solid media laced with cranberry juice.

Methods

Cranberry concentrate at pH 7.0 was added to CFA medium to a final concentration of 25%. E. coli strains JR1 and DS17 were plated on this medium with a plain CFA control and incubated at 37C. Cultures were tested for ability to agglutinate P-receptor specific beads. Bacteria were washed in PBS and agglutination retested. Cultures were also replated on plain CFA agar and rechecked for their ability to agglutinate. Transmission electron micrographs were performed on positive control and test bacteria.

Results

For E. coli strain JR1, P-fimbrial agglutination was inhibited after the third plating. DS17 was fully inhibited after the second plating. Washing in PBS did not affect agglutination, but replating on CFA agar allowed agglutination to recur. Electron micrographic study of control populations confirmed fimbriae. Fully inhibited bacteria had a 100% reduction in expression of fimbriae. Additionally, inhibited bacteria showed cellular elongation.

Conclusions

Cranberry juice irreversibly inhibits P-fimbriae. Electron micrographic evidence suggests that cranberry juice acts on the cell wall preventing proper attachment of the fimbrial subunits or as a genetic control preventing the expression of normal fimbrial subunits or both.     

Relative importance of eight virulence characteristics of pyelonephritogenic Escherichia coli strains assessed by multivariate statistical analysis.

We have previously reported univariate statistical analysis of the prevalences of putative virulence determinants in Escherichia coli isolated from children and adults with acute pyelonephritis. The expression of P-fimbriae, cell surface hydrophobicity, mannose resistant haemagglutination, haemolysin synthesis, cytotoxic necrotizing factor production and aerobactin mediated iron uptake occurred more often in a collection of 115 Escherichia coli strains isolated from children and women with acute non-obstructive pyelonephritis compared to 96 strains isolated from the commensal fecal flora. With the aim to study which of these virulence markers were independently associated with strains causing infection we performed a multivariate statistical analysis with the data from these strains. The previously proposed virulence factors, expression of type 1 fimbriae and adhesion to HeLa cells were also included in the analysis. P-fimbriae, mannose resistant haemagglutination and the production of haemolysin were, in the multivariate analysis, associated with strains isolated from patients with acute pyelonephritis.     

Antibody responses and protection from pyelonephritis following vaccination with purified Escherichia coli PapDG protein

PURPOSE: A critical early step in the establishment of Escherichia coli pyelonephritis is bacterial attachment via the tip protein of P fimbriae. This adhesin, PapG, binds to glycolipid receptors present on vaginal and kidney epithelial surfaces. In this study we investigated the efficacy of vaccination with purified PapDG protein complex in preventing pyelonephritis caused by E. coli. MATERIALS AND METHODS: Mature cynomolgus monkeys were intraperitoneally vaccinated with 100 microg purified PapDG protein. Following 3 identical boosters serum antibody titers to PapDG were measured by enzyme-linked immunosorbent assay. Vaccinated and unvaccinated animals were urethrally inoculated with 1 x 10 cfu of E. coli strain DS17, which was isolated from a child with acute pyelonephritis. The infection course was monitored by catheterized urine cultures, and by histological examination of the kidneys, bladder and kidney tissue culture 28 days after infection. RESULTS: Intraperitoneal administration of purified PapDG vaccine resulted in the development of specific antibody responses in cynomolgus monkeys. In contrast to control monkeys, vaccinated monkeys did not show histological evidence of pyelonephritis after subsequent urethral challenge with pyelonephritogenic E. coli expressing P fimbriae. CONCLUSIONS: Purified PapDG is a tractable vaccine candidate that in our small study demonstrated the ability to elicit adequate serum antibody levels to prevent E. coli mediated pyelonephritis.     

Pathogenic significance of P-fimbriated Escherichia coli in urinary tract infections

The over-all aim of this study was to determine the pathogenic significance, and bacteriological and serological characteristics of P-fimbriated organisms isolated from a general population of patients with bacteriuria. A P-receptor specific particle agglutination test was used to identify P-fimbriated bacteria among 2,010 isolates from male and female patients with bacteriuria (age range infancy to 91 years). Of the 2,010 isolates 206 (10.2 per cent) were positive for P-fimbriae by the P-receptor specific particle agglutination test. Only Escherichia coli was found to be P-fimbriated, with an incidence of 21.5 per cent among 956 Escherichia coli isolates. The critical characteristic of pyelonephritic strains of Escherichia coli was P-fimbriation. In cases of nonobstructive acute pyelonephritis 100 per cent of the infecting bacteria were P-fimbriated. The data indicated clearly that the serotype, biotype, presence of type 1 fimbriae (mannose sensitive), undefined mannose-resistant adhesions, hemolysin production and motility of P-fimbriated Escherichia coli were clinically unimportant differential strain characteristics and not indicative of the virulence of P-fimbriated Escherichia coli within clinical syndromes. Isogenic P-fimbriated Escherichia coli strains were isolated from noncompromised patients in all clinical categories, that is pyelonephritis, asymptomatic bacteriuria and cystitis. A variety of bacterial strains appears to be capable of causing acute pyelonephritis in the presence of obstructive uropathic conditions, regardless of P-fimbriation. Therefore, P-fimbriation becomes a noncritical factor in compromised patients. The P-receptor specific particle agglutination test is a simple and rapid method to determine whether bacteria are P-fimbriated and may be an important screening method to identify those bacteria isolated from individuals at risk for nonobstructive acute pyelonephritis.     

P-fimbriated Escherichia coli and serum antibody responses to P-fimbriae in pregnant women with urinary tract infections and their children

Escherichia coli (E. coli) is still a major pathogen in urinary tract infections (UTI). It was found that 15 out of 20 cases (75%) of E. coli related UTI were caused by P-fimbriated E. coli, compared to the mere 15% of E. coli isolated from urine and 22% from the stool of healthy controls that were P-fimbriated. All patients studied were pregnant women and their delivered children. Antibody responses to P-fimbriae in the sera of these patients were detected with enzyme-linked immunosorbent assay (ELISA) using purified P-fimbriae. Positive antibody responses were observed at titers of 800-6400 in 8 out of 9 cases of UTI of pregnant women caused by P-fimbriated E. coli. The high level of antibody titers persisted for one month on average and then decreased. These antibodies to P-fimbriae were essentially IgG and transmitted to delivered children from UTI mothers. Therefore, the protective role of these antibodies from P-fimbriated E. coli infections in new born children has been suggested.     

Decreased predominance of papG class II allele in Escherichia coli strains isolated from adults with acute pyelonephritis and urinary tract abnormalities

PURPOSE: We compared the genotypes of fimbriae or adhesions of Escherichia coli causing acute pyelonephritis in adults with and without urinary tract abnormalities. MATERIALS AND METHODS: We studied a total of 92 E. coli strains isolated from 54 patients with acute pyelonephritis and a normal urinary tract, and 38 with urinary tract abnormalities. Of those with urinary tract abnormalities 13 with moderate to severe hydronephrosis were also considered a separate group for the purpose of analysis. The genes of 7 known fimbriae or adhesins of E. coli were detected by the polymerase chain reaction, including the papG class I to III alleles (PapG adhesins of P-fimbriae), sfa/foc (S-/F1C-fimbriae), fimH (type 1 fimbriae), and afa (afimbrial adhesin). Virulence genes associated with APN were identified by comparing the prevalence of each of these 7 genes in E. coli strains from 54 patients with acute pyelonephritis with a normal urinary tract to the prevalence in the strains from 37 patients with acute cystitis using univariate and multivariate analysis. Differences in the prevalence of the genes associated with acute pyelonephritis and the incidence of underlying illness were then compared in the 3 acute pyelonephritis groups. RESULTS: On univariate and multivariate analysis the papG class II allele was the only virulence gene associated with acute pyelonephritis (p <0.0001 and 0.001, respectively). No significant difference was noted in the prevalence of underlying medical disease in the 3 acute pyelonephritis groups. The papG class II allele was significantly less predominant in E. coli strains isolated from acute pyelonephritis cases with versus without urinary tract abnormalities (76% versus 93%, p = 0.03). The incidence of the papG class II allele in patients with urinary tract abnormalities and moderate to severe hydronephrosis was less than in those without urinary tract abnormalities (69% versus 93%, p = 0.04). CONCLUSIONS: Our results imply that the papG class II allele has an important role in E. coli infection in patients with acute pyelonephritis and a normal urinary tract, while urinary tract abnormalities and/or obstruction may permit ascending infection of E. coli strains with lower adhesive ability.     

Receptors for Escherichia coli adhesins in the genitourinary tract in a non-human primate

OBJECTIVE: To study the expression of receptors allowing adhesin-mediated binding of Escherichia coli to urogenital tissues ranging from the kidney to the vagina in cynomolgus monkeys using an in situ assay. MATERIAL AND METHODS: Receptors specific for four relevant adhesins were investigated: PapG and PrsG of P-fimbriae binding to gal-alpha(1-4)gal glycosphingolipids (preferentially globoside and the Forssman antigen, respectively): and two variants of FimH of type 1 fimbriae, one binding to monomannose/trimannose and the other to trimannose only. To ascertain the specificity of the observed bindings we used adhesion inhibition by receptor analogues as well as E. coli adhesin knockout mutants. RESULTS: The distributions of PapG and FimH receptors in monkey tissues showed great similarities to available data in humans. Whilst monomannose receptors were expressed on the surface epithelium in both the monkey bladder and ureter, trimannose receptors were not. The different distribution of FimH isoreceptors and the heterogeneity of FimH adhesin variants among E. coli may explain contradictory earlier findings in type 1 fimbriae-mediated adhesion to the human bladder and to renal tissues. We also found evidence of a hitherto unknown type of host-aggressor interaction on vaginal and urethral mucosa, which was not discovered until type 1 fimbriae had been eliminated. CONCLUSIONS: A precise molecular fit between host receptors and bacterial lectins is important in infectious pathogenesis. We conclude that urinary tract infection in the cynomolgus monkey is a relevant model of the human disease because of the similarity in the expression of receptors for E. coli adhesins on epithelial surfaces in the two species.     

P-fimbriae receptors in patients with chronic pyelonephritis

The adherence of fluorescein isothiocyanate-labeled P-fimbriated Escherichia coli to uroepithelial cells from 19 women with chronic pyelonephritis was determined with the fluorescence-activated cell sorting technique. The application of this method has made it possible to study bacterial binding to a large number of cells. Renal function was determined in all patients and the recurrences of P-fimbriated Escherichia coli bacteriuria, cystitis and acute pyelonephritis during a 3-year followup were studied. We found a significant correlation between the P-fimbriae receptor accessibility on uroepithelial cells and glomerular filtration rate (r equals -0.75, p less than 0.001). Uroepithelial cells from the patients with chronic pyelonephritis and renal insufficiency had a higher binding capacity of P-fimbriated Escherichia coli than uroepithelial cells from patients with a normal glomerular filtration rate. There was no correlation between kidney function and the availability of P-fimbriae receptors in a control group of patients with polycystic kidney disease.     

Fimbrial lectins influence the chemokine repertoire in the urinary tract mucosa

The defense against mucosal infections relies on chemokines that recruit inflammatory cells to the mucosa. This study examined if the chemokine response to uro-pathogenic Escherichia coli is influenced by fimbrial expression. The CXC (CXCL1, CXCL5, CXCL8, CXCL9, CXCL10) and CC chemokines (CCL2, CCL3, CCL5) were quantified after in vitro infection of uro-epithelial cells with a fimbriated E. coli pyelonephritis isolate, or with P or type 1 fimbriated transformants of an avirulent E. coli K-12 strain. The response profile was shown to vary with the fimbrial type. Type 1 fimbriated E. coli elicited mainly CXCL1 and CXCL8, whereas P fimbriated E. coli stimulated CCL2 and CCL5 and class II were more potent chemokine inducers than class III P fimbriae. Chemokines were also quantified in urine samples from 73 patients with febrile urinary tract infection, and analyzed as a function of disease severity and fimbrial expression by the strain infecting each patient. A complex CXC and CC chemokine response was detected in patient urine, with a significant influence of the fimbrial type. The results show that virulence factors like fimbriae may modify the mucosal chemokine response. This mechanism may allow the host to adjust the inflammatory cell infiltrate to fit the infecting strain.     

Virulence factors of Escherichia coli contribute to acute renal failure

BACKGROUND: The development of acute renal failure (ARF) significantly enhances the mortality of patients with Gram-negative septic shock. The role of specific bacterial virulence factors different from lipopolysaccharides (LPS) in the deterioration of renal function in septic shock remains to be determined. METHODS: An Escherichia coli wild-type strain (536/21 WT, O6:K15:H31) was isolated from a patient suffering from a urinary tract infection. The strain expresses various virulence factors (e.g. hemolysin, fimbriae) genetically encoded by pathogenicity islands. The spontaneous deletion mutant 536/21 Del lacks the expression of these virulence factors. Isolated rat kidneys were perfused with a suspension (5 x 10(4)/ml) of the respective strain or control perfusion medium and the renal functional parameters were analyzed. Intrarenal deposition of E. coli was detected by immunohistology and Gram staining. RESULTS: The perfusion of the isolated perfused rat kidney with a uropathogenic E. coli wild-type strain (536/21 WT) caused an acute deterioration of renal function which was not observed in kidneys exposed to a deletion mutant of E. coli 536/21 lacking the expression of virulence factors. The glomerular filtration rate and the urine flow rate significantly decreased only in kidneys perfused with the E. coli wild-type strain, while there was no change versus controls in kidneys perfused with the deletion mutant. CONCLUSIONS: Distinctive bacterial virulence factors different from LPS such as hemolysin and the presence of different fimbriae may contribute to the development of ARF in sepsis induced by E. coli. Anti-LPS strategies may not be sufficient to reduce the risk of ARF in Gram-negative septic shock.     

Clinico-bacteriological studies on the etiology of bacterial prostatitis. II. Virulence factors of E. coli in bacterial prostatitis

The virulence factors of E. coli in bacterial prostatitis were studied using 59 E. coli isolated from uncomplicated prostatitis. O-antigens of prostatitis-derived E. coli belonged to some specific serotypes such as 0-4, 6, 18, 22 and the haemolysin production was positive in 64.4%. With regard to the fimbriae, the majority of the strains had type 1 fimbriae (81.4%). Mannose resistant (MR) fimbriae were also positive in 59.3% and both type 1 and MR fimbriae were positive in 55.9%. Among MR strains, P-fimbriated and S-fimbriated strains were present in 25.7% and 28.6%, respectively, indicating that these two MR fimbriae were not always specific for the prostatitis-derived E. coli. Although the specific adhesion of E. coli onto the human prostatic epithelium mediated by MR-fimbriae was equivocal, that mediated by type 1 fimbriae was observed clearly. Therefore, type 1 fimbriae was thought to be one of the most significant virulence factors in the pathogenesis of prostatitis caused by E. coli.     

Experimental prostatitis in nonhuman primates: I. Bacterial adherence in the urethra

Both man and monkey possess urothelial (transitional cell) receptors for P-fimbriae of Escherichia coli; however, the male urethra has pseudostratified columnar cells. We studied adherence using scanning electron microscopy and found that P-fimbriae were the principal mediators of adherence to these cells as well. The monkey, therefore, should be a good model for the study of the ascending route of infection in prostatitis, the route thought to occur in man.     

Virulence of wild-type E. coli uroisolates in experimental pyelonephritis

This study was designed to analyze the colonizing and invasive properties of wild-type bacteriuric E. coli possessing a variety of phenotypic characteristics in experimental nonobstructive pyelonephritis (P and Type 1 [T] fimbriae, hemolysin [Hly], presence of K capsules, flagella [H], serotype, biotype, human and mouse serumcidal resistance). Special emphasis was on the role of Gal-Gal adhesin (P fimbriae) of non-genetically engineered uroisolates. It was shown that organisms that are P+ or T+ or Hly+ are more likely to colonize bladders than strains negative for those parameters (P less than 0.001). Additionally, P+ strains were more often associated with kidney histopathology than P- E. coli (P less than 0.05). However, the data also indicated that fimbriae (P and Type 1) were not sole determinants of virulence since two strains devoid of fimbriae, hemolysin, K capsules and sensitive to human serumcidal activity caused incipient and acute pyelonephritis. Even among identical serotypes and biotypes, the presence/absence of fimbriae did not appear to be the critical factor in urovirulence, nor did the presence of several positive characteristics (hemolysin, K capsule, flagella, serum resistance) in a given strain enhance uropathogenicity. Therefore, these properties do not need to work together to render an E. coli urovirulent. These phenotypic characters may simply represent associated or serologic markers with the host serving as the dominant determinant of susceptibility to urinary infection. The findings emphasize the inherent limitations in relating and extrapolating colonizing and invasive properties of genetically engineered strains to those of naturally occurring, wild-type E. coli human uroisolates causing pyelonephritis.     

Der Einfluss von P-Fimbrien auf eine Leukozyturie und den Schwellenwert einer persistierenden Bakteriurie

This study investigated the role of P fimbriae in colonization of Escherichia coli, host response, and bacterial persistence in humans. Human volunteers were inoculated intravesically with the nonadherent ABU isolate E. coli 83972 and with P fimbriated transformants of the same strain. During the following 24 h all urine samples, and thereafter daily samples, were collected for urine culture, analysis of neutrophil numbers, and cytokine concentrations (IL-6 and IL-8). The P fimbriated transformants showed enhanced bacterial colonization in comparison to E. coli 83972 and lowered the bacterial numbers needed for persistent bacteriuria. The P fimbriated transformants also lowered the bacterial numbers needed for a significant neutrophil and cytokine host response. We conclude that P fimbriae enhance bacterial colonization and trigger the host response in the human urinary tract.     

Pyelonephritic Escherichia coli expressing P fimbriae decrease immune response of the mouse kidney

P fimbriae are proteinaceous appendages on the surface of Escherichia coli bacteria that mediate adherence to uroepithelial cells. E. coli that express P fimbriae account for the majority of ascending urinary tract infections in women with normal urinary tracts. The hypothesis that P fimbriae on uropathic E. coli attach to renal epithelia and may regulate the immune response to establish infection was investigated. The polymeric Ig receptor (pIgR), produced by renal epithelia, transports IgA into the urinary space. Kidney pIgR and urine IgA levels were analyzed in a mouse model of ascending pyelonephritis, using E. coli with (P+) and without (P-) P fimbriae, to determine whether P(+) E. coli regulate epithelial pIgR expression and IgA transport into the urine. (P+) E. coli establish infection and persist to a greater amount than P(-) E. coli. P(+)-infected mice downregulate pIgR mRNA and protein levels compared with P(-)-infected or PBS controls at > or =48 h. The decrease in pIgR was associated with decreased urinary IgA levels in the P(+)-infected group at 48 h. pIgR mRNA and protein also decline in P(+) E. coli-infected LPS-hyporesponsive mice. These studies identify a novel virulence mechanism of E. coli that express P fimbriae. It is proposed that P fimbriae decrease pIgR expression in the kidney and consequently decrease IgA transport into the urinary space. This may explain, in part, how E. coli that bear P fimbriae exploit the immune system of human hosts to establish ascending pyelonephritis.     

Fimch antiserum inhibits the adherence of Escherichia coli to cells collected by voided urine specimens of diabetic women

PURPOSE: With the increasing problem of resistance in pathogenic microorganisms the development of nonantimicrobial therapies is important. Diabetes mellitus (DM) is associated with an increased incidence of urinary tract infections. The majority of Escherichia coli strains, which is the most prevalent uropathogen, have type 1 fimbriae that bind to uroplakin in the bladder, as mediated by the adhesin FimH. A vaccine is being developed based on FimH adhesion. MATERIALS AND METHODS: The sequence of FimH adhesion of 29 E. coli strains isolated from women with DM was determined. For adherence experiments we used E. coli isolated from women with DM and a T24 bladder cell line as well as the 2 well-defined type 1 fimbriated E. coli strains Ctrl 39 and NU14, and uroepithelial cells from women with DM. RESULTS: The fimH sequence of E. coli strains isolated from women with DM was highly homologous to the known fimH sequence of E. coli from patients without DM. Adherence assays in a T24 bladder cell line showed that adherence of these E. coli strains from women with DM could be inhibited by pre-incubation with antiserum raised against the chaperone-adhesin complex FimC-FimH. AntiFimCH antiserum also inhibited the adherence of the 2 well-defined E. coli strains expressing type 1 fimbriae, NU14 and Ctrl 39, but not of the FimH mutant strain NU14 H-, to uroepithelial cells from women with DM. CONCLUSIONS: These findings suggest that a vaccine based on FimH adhesin of type 1 fimbriated E. coli is a potential method of preventing urinary tract infection in women with DM.     

Interaction of multiple risk factors in the pathogenesis of experimental reflux nephropathy in the pig

The importance of several pathogenetic factors in the development of reflux nephropathy was evaluated in 25 piglets with complete unilateral vesicoureteral reflux and urinary tract infection. Three independent risk factors were studied: roentgenographic intrarenal reflux, P-fimbriation of the bacterial strain, absence of previous immunization. E. coli with P-fimbriae produce mannose-resistant agglutination of pig red blood cells and are more adherent to pig uroepithelial cells than E. coli without P-fimbriae. Vesicoureteral reflux was surgically induced at 2 weeks, urinary tract infection introduced at 6 weeks and the animals killed at 12 weeks of age. Independently, the 3 risk factors had a borderline or insignificant effect on renal scarring. Animals with none or only 1 risk factor, however, had significantly less scarring, fewer glomerular lesions and lower serum creatinines than those with 2 or 3 factors present. Several independent pathogenetic factors seem to have a synergistic effect on the development of reflux nephropathy.     

Factors predisposing to urinary tract infections in children

The normal urinary tract is sterile for many reasons. These include: bacterial eradication by urinary and mucus flow, urothelial bactericidal activity, urinary secretory IgA, and blood group antigens in secretions which interfere with bacterial adherence. Periodic emptying of the bladder should wash bacteria out, but uropathogens grow well in urine and their rapid doubling time might not clear bacteria by voiding at the usual frequency. The ability to colonize the gut, as well as adhere to host squamous and urothelial cells, is due to bacterial adherence, a mechanism by which fluid washout would not be effective. Fimbriae or pili, hair-like surface appendages of Escherichia coli, are the usual adhesins. E. coli with type 1 fimbriae adhere to mucus, and P-fimbriae adhere to glycolipids on mucous membranes and urothelial cells. Other common virulence factors of E. coli include the capsule, which prevents phagocytosis, hemolysin, which damages urothelium, and aerobactin, which sequesters iron. Adherence stimulates the inflammatory response by activation of cytokines such as interleukin-1, -6, and -8. These cytokines stimulate the production of intercellular adhesion molecule, which by leukocyte adhesion causes migration of these cells to the site of infection to counteract it. Received September 22, 1995; received in revised form January 22, 1996; accepted January 25, 1996     

Renal Allograft Injury Is Associated with Urinary Tract Infection Caused by Escherichia coli Bearing Adherence Factors

Urinary tract infections are the most common infection in renal transplant patients and Escherichia coli (E. coli) is the most common clinical isolate. Although acute allograft injury (AAI) secondary to urinary tract infection (UTI) has been reported, the incidence of AAI associated with UTI, the virulence factors express by uropathic E. coli and whether virulence factors are associated with renal allograft outcome have not been described. We collected E. coli from our renal transplant patients with UTI, determined O:H serotypes, P and Dr fimbriae expression and the clinical presentation and allograft function during the UTI and post-UTI period. Pyelonephritis occurred in 40% of our patients, 82% of which had AAI (>20% increase in SCr). Sixty-two percent of E. coli isolates that expressed P fimbriae were associated with AAI, whereas only 29% that did not express P fimbriae had AAI (p = 0.03). The pattern of P fimbriae and O serotypes differed from reported isolates, as the P fimbriae PapG class II and the O25 serotype were the most common. Dr adhesin was expressed on 7 isolates, including 2 of 3 with urosepsis. We propose a unique pattern of uropathogenic serotypes and adherence factors contribute to acute allograft injury in renal transplant patients with UTI.