Hugh Connell

P fimbriae enhance the early establishment of Escherichia coli in the human urinary tract.

This study examined the role of P fimbriae in the establishment of bacteriuria. Patients (n = 17) were subjected to intravesical inoculation with an asymptomatic bacteriuria strain, Escherichia coli 83972, or its P‐fimbriated (pap+/prs+) transformants. As shown by groupwise analysis, the pap+/prs+ transformants established bacteriuria more rapidly than E. coli 83972 (P = 0.021) and required a lower number of inoculations to reach 105 cfu ml−1 (P = 0.018). Intraindividual analysis showed that the pap+/prs+ transformants established bacteriuria more rapidly than E. coli 83972 in the patients who subsequently became carriers of both strains. Finally, bacterial establishment was shown to vary with the in vivo expression of P fimbriae. Bacterial counts were higher when P‐fimbrial expression was detected than when the pap+/prs+ strain showed a negative phenotype. The results suggested that P fimbriae enhance the establishment of bacteriuria and fulfil the molecular Koch postulates as a colonization factor in the human urinary tract.

P-fimbriae trigger mucosal responses to Escherichia coli in the human urinary tract.

Uropathogenic Escherichia coli elicit a host response that determines the severity of urinary tract infection (UTI). Specific adherence mechanisms allow the bacteria to initiate this process by targeting epithelial cells in the urinary tract mucosa. Epidemiological studies show a strong association of P‐fimbriae with disease severity, suggesting that adherence mediated by these organelles has a direct effect on mucosal inflammation in vivo. The present study examined the ability of P‐fimbriae to induce inflammation in the human urinary tract. Patients were subjected to intravesical inoculation with a non‐fimbriated E. coli strain or transformants of this strain expressing P‐fimbriae. The inflammatory response was analysed as a function of P‐fimbrial expression. The P‐fimbriated transformants invariably caused higher interleukin (IL)‐8, IL‐6 and neutrophil responses in the urinary tract than the ABU strain. Furthermore, loss of P‐fimbrial expression in vivo was accompanied by a return to background levels of neutrophils, IL‐6 and IL‐8 in individual patients. The results demonstrate that the pap sequences confer on a non‐fimbriated, avirulent strain the ability to induce a host response in the human urinary tract. P‐fimbriae thus fulfil the ‘molecular Koch–Henle postulates’ linking a single virulence factor to host response induction.

URODYNAMIC FACTORS INFLUENCE THE DURATION OF ESCHERICHIA COLI BACTERIURIA IN DELIBERATELY COLONIZED CASES

PURPOSE We evaluated the influence of urodynamic factors on the establishment of bacteriuria, after deliberate intravesical inoculation with Escherichia coli. MATERIALS AND METHODS Nine women and 7 men with recurrent symptomatic urinary tract infections underwent intravesical injection of E. coli 83972. This strain had documented ability to persist in the urinary tract and it lacks expressed virulence factors associated with urinary tract infection. RESULTS Successful long-term colonization (5 months to 3 years) was achieved in 6 of 12 patients with neurogenic bladder disorder, including normal or high bladder capacity, normal or low detrusor pressure and residual urine. Short-term bacteriuria (13 days) occurred in 1 but long-term bacteriuria was not established in the 4 patients with normal lower urinary tract function. Occasionally urine samples from the colonized patients contained other bacterial strains, which cleared spontaneously except for a Klebsiella strain that became established in 2 and subsequently eliminated E. coli 83972. CONCLUSIONS E. coli 83972 bacteriuria could only be established in a subset of patients with defective bladder voiding, suggesting that urodynamic defects permit a nonvirulent strain to establish in the urinary tract, but that additional host factors determine if bacteriuria will persist.

Bacterial Attachment To Uro-Epithelial Cells: Mechanisms and Consequences

Microbial attachment to mucosal surfaces is a first step in mucosal infection. Specific interactions between microbial surface ligands and host receptors influence the distribution of microbes in their sites of infection. Adhesion has often been regarded as a sufficient end point, explaining tissue tropism and bacterial persistence at mucosal sites. Adherence, however, is also a virulence factor through which microbes gain access to host tissues, upset the integrity of the mucosal barrier, and cause disease. The induction of mucosal inflammation is one aspect of this process. Bacterial attachment to mucosal surfaces activates the production of pro-inflammatory cytokines that cause both local and systemic inflammation. Epithelial cells are one source of these cytokines. The binding of fimbrial lectins to epithelial cell receptors triggers transmembrane signaling events that upregulate cytokine-specific mRNA and increase cytokine secretion. P fimbriae that bind the globoseries of glycolipids cause the release of ceramides and activation of the ceramide signaling pathway which contributes to the IL-6 response. Spread of cytokines and other pro-inflammatory mediators from the local site contributes to the symptoms and signs of infection.

Expression of type 1 and P fimbriae in situ and localisation of a uropathogenic Escherichia coli strain in the murine bladder and kidney.

Adhesion is an important aspect of bacterial colonisation and induction of human disease. Escherichia coli which infects and causes disease of the urinary tract expresses several adherence factors including type 1 and P fimbriae. Their expression has been implicated in the virulence of E. coli strains infecting the urinary tract, however, the evidence for the expression of these fimbriae in situ has been implied rather than proven. Here we describe in situ detection of E. coli and of fimbrial expression in urinary tract tissue. Kidneys and bladders were isolated from mice infected with the uropathogenic isolate E. coli AD110. The tissue was sectioned and subjected to DNA-rRNA hybridization and indirect immunofluorescent staining with antibodies against type 1 and P fimbriae. Sections of both kidney and bladder stained positive for bacterial cells using a Cy3-labelled E. coli-specific rRNA probe. The same cells in these sections also stained positive for type 1 or P fimbriae using fluorescein-labelled antibodies. Tissue taken from several different time points (2, 6, and 24 hours post infection) showed the presence of bacterial cells which stained positive for fimbrial expression. Bacteria in kidney and bladder sections were observed either as individual cells associated with the mucosa or as members of microcolonies.

Fimbriae—Mediated Adherence Induces Cosal Inflammation and Bacterial Clearance

Escherichia colistrains express a variety of fimbrial and non-fimbrial adherence factors which bind via lectin-receptor interactions to host cell glycoconjugate receptors. The attached state provides several advantages; it allows bacteria to resist elimination by the flow of secretions, it enhances their ability to trap nutrients, to multiply and to colonize the mucosa. Attachment may indeed be the endpoint for microbes that form part of the indigenous flora at different mucosal sites. For the pathogens however, adherence is only the first step in a complex series of events that lead to disease. The pathogens may activate the mucosal cells to which they bind, may invade into and through those cells, and may disrupt the integrity of the mucosal cell layer to reach underlying tissue compartments. Common to these events is the induction of an inflammatory response in the mucosa.