Type 1 fimbrial expression enhances Escherichia coli virulence for the urinary tract.

Connell, I; Agace, William W.; Klemm, Per; Schembri, Mark A.; Mårild, Staffan; Svanborg, Catharina

doi:10.1073/pnas.93.18.9827

Cited by 657 publications

(560 citation statements)

References 44 publications

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“…Type 1-mediated adherence has been proposed to play a role in the induction of inflammation, enhancing E. coli virulence for the urinary tract. CONNELL et al, (1996) 4 reported that mice infected with a type 1-positive 01:K1:H7 isolate showed a higher urinary neutrophil influx into the urine than type 1-negative isolates. Furthermore, we demonstrated that 76 fimH strains, occurred with at least one adhesin, such as pap, sfa, or afa.…”

Section: Discussionmentioning

confidence: 99%

Genotypic characterization of virulence factors in Escherichia coli strains from patients with cystitis

Tiba

Yano

Leite

2008

Rev. Inst. Med. trop. S. Paulo

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Abbreviations: aerobactin (iucD), afimbrial adhesin (afaB/C), cytolethal distending toxin (cdtB), cytotoxic necrotizing factor type 1 (cnf-1), G adhesin classes of P fimbriae (papG alleles), group II capsule (kpsMTII), α-hemolysin (hly), minor structural subunits of P fimbriae (papE/F), outer membrane protein of P fimbrae (papC), polymerase chain reaction (PCR), S fimbriae (sfaC/D), type 1 fimbriae (fimH), urinary tract infection (UTI), uropathogenic specific protein (usp), uropathogenic Escherichia coli (UPEC), virulence factors (VFs SUMMARYAdhesins (P-fimbriae, S-fimbriae, type 1 fimbriae and afimbrial adhesin), toxins (α-hemolysin and cytotoxic necrotizing factor type 1), iron acquisition systems (aerobactin) and host defense avoidance mechanisms (capsule or lipopolysaccharide) have been shown to be prevalent in Escherichia coli strains associated with urinary tract infections. In this work, 162 Uropathogenic Escherichia coli (UPEC) strains from patients with cystitis were genotypically characterized by polymerase chain reaction (PCR) assay. We developed three multiplex PCR assays for virulence-related genes papC, papE /F, papG alleles, fimH, sfa/foc, afaE, hly, usp, cdtB, iucD, and kpsMTII, all

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Section: Discussionmentioning

confidence: 99%

Genotypic characterization of virulence factors in Escherichia coli strains from patients with cystitis

Tiba

Yano

Leite

2008

Rev. Inst. Med. trop. S. Paulo

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“…Type 1 fimbriae bind to mannosylated glycoproteins rather than glycosphingolipids and have been shown to adhere efficiently to the murine uro-epithelium and to activate the innate host response in the murine urinary tract [21]. Experimental UTI was established in C57BL/6 Tlr4 WT/ WT or Tlr4 -/-mice with E. coli S1918 fim + or the fimvector control (Fig.…”

Section: Type 1 Fimbriated E Coli Involve Tlr4 and Myd88mentioning

confidence: 99%

“…The host cell receptors for P are glycosphingolipids, and the PapG tip adhesin binds to oligosaccharide receptor epitopes, which are abundantly expressed in the human urinary tract mucosa [19,20]. Type 1 fimbriae differ in receptor specificity, as they recognise mannosylated glycoproteins rather than glycosphingolipids, but both P and type 1 fimbriae trigger the innate host response in the murine urinary tract [21][22][23][24]. In addition, P fimbriae are sufficient to stimulate the innate host response in the human urinary tract and thus fulfil the molecular Koch postulates as independent virulence factors in vivo [25,26].…”

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confidence: 99%

Mechanism of pathogen‐specific TLR4 activation in the mucosa: Fimbriae, recognition receptors and adaptor protein selection

et al. 2006

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The mucosal host defence discriminates pathogens from commensals, and prevents infection while allowing the normal flora to persist. Paradoxically, Toll-like receptors (TLR) control the mucosal defence against pathogens, even though the TLR recognise conserved molecules like LPS, which are shared between pathogens and commensals. This study proposes a mechanism of pathogen-specific mucosal TLR4 activation, involving adhesive ligands and their host cell receptors. TLR4 signalling was activated in CD14-negative, LPS-unresponsive epithelial cells by P fimbriated, uropathogenic Escherichia coli but not by a mutant lacking fimbriae. Epithelial TLR4 signalling in vivo involved the glycosphingolipid receptors for P fimbriae and the adaptor proteins Toll/IL-1R (TIR) domain-containing adaptor inducing IFN-b (TRIF)/TRIF-related adaptor molecule (TRAM), but myeloid differentiation protein 88 (MyD88)/TIR domain-containing adaptor protein were not required for the epithelial response. Substituting the P fimbriae with type 1 fimbriae changed TLR4 signalling from the TRIF to the MyD88 adaptor pathway. In addition, the adaptor proteins and the fimbrial type were found to influence bacterial clearance. Trif -/-and Tram -/-mice remained infected with P fimbriated E. coli but cleared thetype 1 fimbriated strain, while Myd88 -/-mice became carriers of both the P and the type 1 fimbriated bacteria. Thus, TLR4 may be engaged specifically by pathogens, when the proper cell surface receptors are engaged by virulence ligands. IntroductionToll-like receptors (TLR) control the innate host defence at mucosal surfaces and yet commensals do not induce an inflammatory response at those sites. The relative inertia to the commensals is paradoxical, as the TLR recognise conserved pathogen-associated molecular patterns (PAMP), which are present on both pathogenic and commensal bacteria. Lipolysaccharide (LPS), flagellin, peptidoglycan or DNA may bind directly to the TLR but in addition, co-receptors are needed to enhance the TLR response to these conserved ligands [1][2][3]. Myeloid cells use CD14 and MD-2 as co-receptors for LPS in TLR4 signalling, and minute amounts of LPS may elicit a strong systemic inflammatory response [4,5]. However, the TLR response to pathogen attack at mucosal surfaces is controlled by different interactions. Epithelial cells must be protected from constant TLR activation by commensals and their PAMP, in order for mucosal integrity to be maintained. The epithelial cells thus lack co-receptors like CD14 [6][7][8][9][10][11], and in addition, commensals have been suggested to actively suppress epithelia responses through NF-jB [12,13]. Yet, mucosal pathogens evoke rapid TLR4-dependent responses at mucosal sites, suggesting that alternative ligands and receptors might be involved in mucosal TLR activation. Pathogens use adhesive surface ligands to break the inertia of the mucosal barrier [14][15][16]. The innate defence is activated as a direct result of these interactions and epithelial cells produce the first wave of me...

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“…The expression and binding of these various adhesins to epithelial cell receptors determine tissue specificity and allow UPEC isolates to ascend to the lower urinary tract and the kidney in experimental models of UTI (3)(4)(5)(6)(7)(8).…”

Section: Renal Collecting Duct Epithelial Cells React Tomentioning

confidence: 99%

Renal Collecting Duct Epithelial Cells React to Pyelonephritis-Associated Escherichia coli by Activating Distinct TLR4-Dependent and -Independent Inflammatory Pathways

Chassin

Goujon

Darche³

et al. 2006

The Journal of Immunology

119

156

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TLR4 plays a central role in resistance to pyelonephritis caused by uropathogenic Escherichia coli (UPEC). It has been suggested that renal tubule epithelial cells expressing TLRs may play a key role in inflammatory disorders and in initiating host defenses. In this study we used an experimental mouse model of ascending urinary tract infection to show that UPEC isolates preferentially adhered to the apical surface of medullary collecting duct (MCD) intercalated cells. UPEC-infected C3H/HeJ (Lpsd) mice carrying an inactivating mutation of tlr4 failed to clear renal bacteria and exhibited a dramatic slump in proinflammatory mediators as compared with infected wild-type C3H/HeOuJ (Lpsn) mice. However, the level of expression of the leukocyte chemoattractants MIP-2 and TNF-α still remained greater in UPEC-infected than in naive C3H/HeJ (Lpsd) mice. Using primary cultures of microdissected Lpsn MCDs that expressed TLR4 and its accessory molecules MD2, MyD88, and CD14, we also show that UPECs stimulated both a TLR4-mediated, MyD88-dependent, TIR domain-containing adaptor-inducing IFN-β-independent pathway and a TLR4-independent pathway, leading to bipolarized secretion of MIP-2. Stimulation by UPECs of the TLR4-mediated pathway in Lpsn MCDs leads to the activation of NF-κB, and MAPK p38, ERK1/2, and JNK. In addition, UPECs stimulated TLR4-independent signaling by activating a TNF receptor-associated factor 2-apoptosis signal-regulatory kinase 1-JNK pathway. These findings demonstrate that epithelial collecting duct cells are actively involved in the initiation of an immune response via several distinct signaling pathways and suggest that intercalated cells play an active role in the recognition of UPECs colonizing the kidneys.

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Type 1 fimbrial expression enhances Escherichia coli virulence for the urinary tract.

Cited by 657 publications

References 44 publications

Genotypic characterization of virulence factors in Escherichia coli strains from patients with cystitis

Genotypic characterization of virulence factors in Escherichia coli strains from patients with cystitis

Mechanism of pathogen‐specific TLR4 activation in the mucosa: Fimbriae, recognition receptors and adaptor protein selection

Renal Collecting Duct Epithelial Cells React to Pyelonephritis-Associated Escherichia coli by Activating Distinct TLR4-Dependent and -Independent Inflammatory Pathways

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