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.

Rice JC ，Peng T ，Spence JS ，Wang HQ ，Goldblum RM ，Corthésy B ，Nowicki BJ ... -  《JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY》

Do type 1 fimbriae promote inflammation in the human urinary tract?

Type 1 fimbriae have been implicated as virulence factors in animal models of urinary tract infection (UTI), but the function in human disease remains unclear. This study used a human challenge model to examine if type 1 fimbriae trigger inflammation in the urinary tract. The asymptomatic bacteriuria strain Escherichia coli 83972, which fails to express type 1 fimbriae, due to a 4.25 kb fimB-fimD deletion, was reconstituted with a functional fim gene cluster and fimbrial expression was monitored through a gfp reporter. Each patient was inoculated with the fim+ or fim- variants on separate occasions, and the host response to type 1 fimbriae was quantified by intraindividual comparisons of the responses to the fim+ or fim- isogens, using cytokines and neutrophils as end-points. Type 1 fimbriae did not promote inflammation and adherence was poor, as examined on exfoliated cells in urine. This was unexpected, as type 1 fimbriae enhanced the inflammatory response to the same strain in the murine urinary tract and as P fimbrial expression by E. coli 83972 enhances adherence and inflammation in challenged patients. We conclude that type 1 fimbriae do not contribute to the mucosal inflammatory response in the human urinary tract.

Bergsten G ，Wullt B ，Schembri MA ，Leijonhufvud I ，Svanborg C ... -  《CELLULAR MICROBIOLOGY》

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

We compared the genotypes of fimbriae or adhesions of Escherichia coli causing acute pyelonephritis in adults with and without urinary tract abnormalities. 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. 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). 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.

Tseng CC ，Huang JJ ，Ko WC ，Yan JJ ，Wu JJ ... -  《JOURNAL OF UROLOGY》

Tamm-Horsfall protein inhibits binding of S- and P-fimbriated Escherichia coli to human renal tubular epithelial cells.

Escherichia coli is the predominant pathogen in urinary tract infections. Fimbriae are one of the major virulence factors of these bacteria, since these protein appendices contribute towards bacterial adhesion to epithelial cells. In clinical E. coli isolates from urinary tract infections, P fimbriae are more frequently present than S fimbriae. However, these two types of fimbriae mediate adhesion to cultured tubular epithelial cells equally well. Tamm-Horsfall protein, which is the most abundant protein in normal human urine, inhibits hemagglutination by E. coli expressing S fimbriae, but does not interfere with hemagglutination by P-fimbriated E. coli. Therefore, it has been speculated that Tamm-Horsfall protein may serve as a clearance factor for S-fimbriated E. coli in human urine. In our experiments, adherence of purified S fimbriae and of S-fimbriated E. coli to tubular epithelial cells was inhibited by Tamm-Horsfall protein, but the protein also decreased binding of P-fimbriated E. coli to approximately the same degree. We found less adherence of both types of fimbriae to a Madin-Darby canine kidney cell line expressing soluble and membrane-bound Tamm-Horsfall protein as compared with the control cell line. In conclusion, our in vitro data suggest that urinary Tamm-Horsfall protein may serve as a clearance factor for E. coli expressing both S and P fimbriae. In the light of these findings, the low clinical relevance of S-fimbriated E. coli for urinary tract infections may be readily explained; however, the predominance of P fimbriae remains unresolved.

Leeker A ，Kreft B ，Sandmann J ，Bates J ，Wasenauer G ，Múller H ，Sack K ，Kumar S ... -  《experimental nephrology》

Blocking adherence of uropathogenic Escherichia coli isolate to HEP-2 cells and bladder of mice in the presence of antibody against p-fimbriae.

Presence of fimbriae on Escherichia coli isolated from the urine of patients with urinary tract infection was related to the ability of the bacteria to attach to human uroepithelial cells. One of the 50 isolates that expresses high MRHA p-fimbriae, selected and antibody against p-fimbriae from it, showed blocking of attachment of bacteria to HEP-2 cell in 1:1024 titer. Also, 1:512 titer of this antiserum to blocking of attachment in bladder tissue of mice is significant.

Bidhendi SM ，Sattari M ，Pourbakhsh SA ，Mobarez A ，Vandyousefi J ，Khaki P ，Heidari MH ，Kazemnejad A ... -  《BIOLOGICALS》