Protection against Escherichia coli-induced urinary tract infections with hybridoma antibodies directed against type 1 fimbriae or complementary D-mannose receptors.

Bacterial fimbriae are an important virulence factor mediating adhesion to both biotic and abiotic surfaces and facilitating biofilm formation. The expression of type 1 fimbriae of Escherichia coli is a key virulence factor for urinary tract infections and catheter-associated urinary tract infections, which represent the most common nosocomial infections. New strategies to reduce adhesion of bacteria to surfaces is therefore warranted. The aim of the present study was to investigate how surfaces with different nanotopography-influenced fimbriae-mediated adhesion. Surfaces with three different nanopattern surface coverages made in polycarbonate were fabricated by injection molding from electron beam lithography nanopatterned templates. The surfaces were constructed with features of approximately 40 nm width and 25 nm height with 100 nm, 250 nm, and 500 nm interspace distance, respectively. The role of fimbriae type 1-mediated adhesion was investigated using the E. coli wild type BW25113 and ΔfimA (with a knockout of major pilus protein FimA) and ΔfimH (with a knockout of minor protein FimH) mutants. For the surfaces with nanotopography, all strains adhered least to areas with the largest interpillar distance (500 nm). For the E. coli wild type, no difference in adhesion between surfaces without pillars and the largest interpillar distance was observed. For the deletion mutants, increased adhesion was observed for surfaces without pillars compared to surfaces with the largest interpillar distance. The presence of a fully functional type 1 fimbria decreased the bacterial adhesion to the nanopatterned surfaces in comparison to the mutants.

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Altered Regulation of the Diguanylate Cyclase YaiC Reduces Production of Type 1 Fimbriae in a Pst Mutant of Uropathogenic Escherichia coli CFT073

Journal of Bacteriology ◽

10.1128/jb.00168-17 ◽

2017 ◽

Vol 199 (24) ◽

Cited By ~ 7

Author(s):

Sébastien Crépin ◽

Gaëlle Porcheron ◽

Sébastien Houle ◽

Josée Harel ◽

Charles M. Dozois

Keyword(s):

Escherichia Coli ◽

Urinary Tract ◽

Molecular Mechanisms ◽

Diguanylate Cyclase ◽

Altered Expression ◽

Content Type ◽

Type 1 Fimbriae ◽

Tract Infections ◽

Pst System

ABSTRACT The pst gene cluster encodes the phosphate-specific transport (Pst) system. Inactivation of the Pst system constitutively activates the two-component regulatory system PhoBR and attenuates the virulence of pathogenic bacteria. In uropathogenic Escherichia coli strain CFT073, attenuation by inactivation of pst is predominantly attributed to the decreased expression of type 1 fimbriae. However, the molecular mechanisms connecting the Pst system and type 1 fimbriae are unknown. To address this, a transposon library was constructed in the pst mutant, and clones were tested for a regain in type 1 fimbrial production. Among them, the diguanylate cyclase encoded by yaiC (adrA in Salmonella) was identified to connect the Pst system and type 1 fimbrial expression. In the pst mutant, the decreased expression of type 1 fimbriae is connected by the induction of yaiC. This is predominantly due to altered expression of the FimBE-like recombinase genes ipuA and ipbA, affecting at the same time the inversion of the fim promoter switch (fimS). In the pst mutant, inactivation of yaiC restored fim-dependent adhesion to bladder cells and virulence. Interestingly, the expression of yaiC was activated by PhoB, since transcription of yaiC was linked to the PhoB-dependent phoA-psiF operon. As YaiC is involved in cyclic di-GMP (c-di-GMP) biosynthesis, an increased accumulation of c-di-GMP was observed in the pst mutant. Hence, the results suggest that one mechanism by which deletion of the Pst system reduces the expression of type 1 fimbriae is through PhoBR-mediated activation of yaiC, which in turn increases the accumulation of c-di-GMP, represses the fim operon, and, consequently, attenuates virulence in the mouse urinary tract infection model. IMPORTANCE Urinary tract infections (UTIs) are common bacterial infections in humans. They are mainly caused by uropathogenic Escherichia coli (UPEC). We previously showed that interference with phosphate homeostasis decreases the expression of type 1 fimbriae and attenuates UPEC virulence. Herein, we identified that alteration of the phosphate metabolism increases production of the signaling molecule c-di-GMP, which in turn decreases the expression of type 1 fimbriae. We also determine the regulatory cascade leading to the accumulation of c-di-GMP and identify the Pho regulon as new players in c-di-GMP-mediated cell signaling. By understanding the molecular mechanisms leading to the expression of virulence factors, we will be in a better position to develop new therapeutics.

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Uropathogenic Escherichia coli Triggers Oxygen-Dependent Apoptosis in Human Neutrophils through the Cooperative Effect of Type 1 Fimbriae and Lipopolysaccharide

Infection and Immunity ◽

10.1128/iai.72.8.4570-4578.2004 ◽

2004 ◽

Vol 72 (8) ◽

pp. 4570-4578 ◽

Cited By ~ 39

Author(s):

Robert Blomgran ◽

Limin Zheng ◽

Olle Stendahl

Keyword(s):

Escherichia Coli ◽

Urinary Tract ◽

Human Neutrophils ◽

Dependent Manner ◽

E Coli ◽

Type 1 Fimbriae ◽

The Difference ◽

Tract Infections ◽

Neutrophil Survival

ABSTRACT Type 1 fimbriae are the most commonly expressed virulence factor on uropathogenic Escherichia coli. In addition to promoting avid bacterial adherence to the uroepithelium and enabling colonization, type 1 fimbriae recruit neutrophils to the urinary tract as an early inflammatory response. Using clinical isolates of type 1 fimbriated E. coli and an isogenic type 1 fimbria-negative mutant (CN1016) lacking the FimH adhesin, we investigated if these strains could modulate apoptosis in human neutrophils. We found that E. coli expressing type 1 fimbriae interacted with neutrophils in a mannose- and lipopolysaccharide (LPS)-dependent manner, leading to apoptosis which was triggered by the intracellular generation of reactive oxygen species. This induced neutrophil apoptosis was abolished by blocking FimH-mediated attachment, by inhibiting NADPH oxidase activation, or by neutralizing LPS. In contrast, CN1016, which did not adhere to or activate the respiratory burst of neutrophils, delayed the spontaneous apoptosis in an LPS-dependent manner. This delayed apoptosis could be mimicked by adding purified LPS and was also observed by using fimbriated bacteria in the presence of d-mannose. These results suggest that LPS is required for E. coli to exert both pro- and antiapoptotic effects on neutrophils and that the difference in LPS presentation (i.e., with or without fimbriae) determines the outcome. The present study showed that there is a fine-tuned balance between type 1 fimbria-induced and LPS-mediated delay of apoptosis in human neutrophils, in which altered fimbrial expression on uropathogenic E. coli determines the neutrophil survival and the subsequent inflammation during urinary tract infections.

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Decreased Expression of Type 1 Fimbriae by apstMutant of Uropathogenic Escherichia coli Reduces Urinary Tract Infection

Infection and Immunity ◽

10.1128/iai.00162-12 ◽

2012 ◽

Vol 80 (8) ◽

pp. 2802-2815 ◽

Cited By ~ 34

Author(s):

Sébastien Crépin ◽

Sébastien Houle ◽

Marie-Ève Charbonneau ◽

Michaël Mourez ◽

Josée Harel ◽

...

Keyword(s):

Escherichia Coli ◽

Urinary Tract ◽

Bacterial Virulence ◽

Pho Regulon ◽

Upec Strain ◽

Content Type ◽

Type 1 Fimbriae ◽

Genes Encoding ◽

Tract Infections

ABSTRACTThepstSCAB-phoUoperon encodes the phosphate-specific transport system (Pst). Loss of Pst constitutively activates the Pho regulon and decreases bacterial virulence. However, specific mechanisms underlying decreased bacterial virulence through inactivation of Pst are poorly understood. In uropathogenicEscherichia coli(UPEC) strain CFT073, inactivation ofpstdecreased urinary tract colonization in CBA/J mice. Thepstmutant was deficient in production of type 1 fimbriae and showed decreased expression of thefimAstructural gene which correlated with differential expression of thefimB,fimE,ipuA, andipbAgenes, encoding recombinases, mediating inversion of thefimpromoter. The role offimdownregulation in attenuation of thepstmutant was confirmed using afimphase-locked-on derivative, which demonstrated a significant gain in virulence. In addition, thepstmutant was less able to invade human bladder epithelial cells. Since type 1 fimbriae contribute to UPEC virulence by promoting colonization and invasion of bladder cells, the reduced bladder colonization by thepstmutant is predominantly attributed to downregulation of these fimbriae. Elucidation of mechanisms mediating the control of type 1 fimbriae through activation of the Pho regulon in UPEC may open new avenues for therapeutics or prophylactics against urinary tract infections.

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The characterization of multidrug resistant type 1 S-fimbriated Escherichia coli from women with recurrent urinary tract infections (RUTIS) in Bangladesh

African Journal of Clinical and Experimental Microbiology ◽

10.4314/ajcem.v20i1.4 ◽

2018 ◽

Vol 20 (1) ◽

pp. 25

Author(s):

M. K. Hasan ◽

F. Momtaz ◽

M.J. Foysal ◽

M.H. Ali ◽

K. Islam ◽

...

Keyword(s):

Escherichia Coli ◽

Urinary Tract ◽

Urinary Tract Infections ◽

Multidrug Resistant ◽

Recurrent Urinary Tract Infections ◽

Tract Infections

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Establishment of a Persistent Escherichia coli Reservoir during the Acute Phase of a Bladder Infection

Infection and Immunity ◽

10.1128/iai.69.7.4572-4579.2001 ◽

2001 ◽

Vol 69 (7) ◽

pp. 4572-4579 ◽

Cited By ~ 474

Author(s):

Matthew A. Mulvey ◽

Joel D. Schilling ◽

Scott J. Hultgren

Keyword(s):

Escherichia Coli ◽

Urinary Tract ◽

Epithelial Cells ◽

Urinary Tract Infections ◽

Bacterial Attachment ◽

Bacterial Invasion ◽

E Coli ◽

Bladder Cells ◽

Tract Infections

ABSTRACT The vast majority of urinary tract infections are caused by strains of uropathogenic Escherichia coli that encode filamentous adhesive organelles called type 1 pili. These structures mediate both bacterial attachment to and invasion of bladder epithelial cells. However, the mechanism by which type 1 pilus-mediated bacterial invasion contributes to the pathogenesis of a urinary tract infection is unknown. Here we show that type 1-piliated uropathogens can invade the superficial epithelial cells that line the lumenal surface of the bladder and subsequently replicate, forming massive foci of intracellular E. coli termed bacterial factories. In response to infection, superficial bladder cells exfoliate and are removed with the flow of urine. To avoid clearance by exfoliation, intracellular uropathogens can reemerge and eventually establish a persistent, quiescent bacterial reservoir within the bladder mucosa that may serve as a source for recurrent acute infections. These observations suggest that urinary tract infections are more chronic and invasive than generally assumed.

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