The role of P fimbriae for Escherichia coli establishment and mucosal inflammation in the human urinary tract (original) (raw)
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Deliberate Establishment of Asymptomatic Bacteriuria—A Novel Strategy to Prevent Recurrent UTI
Pathogens, 2016
We have established a novel strategy to reduce the risk for recurrent urinary tract infection (UTI), where rapidly increasing antibiotic resistance poses a major threat. Epidemiologic studies have demonstrated that asymptomatic bacteriuria (ABU) protects the host against symptomatic infections with more virulent strains. To mimic this protective effect, we deliberately establish ABU in UTI-prone patients, who are refractory to conventional therapy. The patients are inoculated with Escherichia coli (E. coli) 83972, now widely used as a prototype ABU strain. Therapeutic efficacy has been demonstrated in a placebo-controlled trial, supporting the feasibility of using E. coli 83972 as a tool to prevent recurrent UTI and, potentially, to outcompete antibiotic-resistant strains from the human urinary tract. In addition, the human inoculation protocol offers unique opportunities to study host-parasite interaction in vivo in the human urinary tract. Here, we review the clinical evidence for protection using this approach as well as some molecular insights into the pathogenesis of UTI that have been gained during these studies.
Stamford Journal of Microbiology, 2015
With the previous knowledge on the production of ?-lactamase by the bacterial pathogens causing urinary tract infection, present study further investigated the presence of symptomatic and asymptomatic bacteriuria in female patients admitted into the Delta Medical College with suspected urinary tract infections (UTIs). The manifestation of uropathogens and their responses against locally available antibiotics (amoxicillin, 10 ?g; cephradin, 30 ?g; ciprofloxacin, 5 ?g; cotrimoxazole, 23.8 ?g; gentamicin, 10 ?g; nalidixic acid, 30 ?g) were inquired by means of conventional cultural techniques and double-disc diffusion methods, respectively. Among 110 urine samples collected from the patients with suspected UTI, 34 were found to be culture positive. Symptomatic (64.7%) and asymptomatic (36.3%) bacteriuria were noticed inside the puss cell of the UTI positive cases. Escherichia coli (73.5%) was the dominant bacteria while Klebsiella spp. (26.5%) was also exultant. Around 96% uropathogens...
International Journal of Medical Microbiology, 2005
Urinary tract infections (UTI) are among the most common bacterial infections in humans. Symptomatic UTIs may be acute, recurrent or chronic but the most frequent form of UTI is asymptomatic bacteruria (ABU). In ABU, the mucosa remains inert, despite the presence of large bacterial numbers in urine. The difference in disease severity reflects the virulence of the infecting strain and the propensity of the host to respond to infection. It is essential to understand the molecular basis of disease diversity and the molecular interactions between bacteria and host that determine asymptomatic carriage and the transition to disease. We discuss the initial interactions between bacteria and the mucosal surfaces in the human urinary tract, and the bacterial factors involved in the breach of mucosal inertia. Specifically, the contribution of P and type 1 fimbriae to bacterial establishment and host response induction are investigated. The results show that P fimbriae serve as independent virulence factors when expressed by an ABU strain, by promoting the establishment of bacteriuria and the innate host response, which is the cause of symptoms and tissue damage. P fimbriae thus fulfil the molecular Koch postulates as independent virulence factors in the human urinary tract. Type 1 fimbriae, in contrast, did not act as virulence factors in this model, and thus appear to serve a different function in man than in the murine model.
Urinary tract infections: new insights into a common problem
Postgraduate Medical Journal, 2005
U rinary tract infection (UTI) is one of the most common bacterial infections encountered in clinical practice in Europe and North America. It is estimated that 150 million cases of UTI occur on a global basis per year resulting in more than 4 billion pounds (6 billion dollars) in direct health care expenditure. 1 Young, otherwise healthy, women are commonly affected with an estimated incidence of 0.5-0.7 infections per year. 2 Of the women affected 25%-30% will go on to develop recurrent infections not related to any functional or anatomical urinary tract abnormality. Although uncomplicated infections do not result in long term sequelae, for example renal scarring, they cause significant morbidity, particularly when recurrent.
Asymptomatic Bacteriuria Escherichia coli Are Live Biotherapeutics for UTI
PLoS ONE, 2014
Urinary tract infections (UTI) account for approximately 8 million clinic visits annually with symptoms that include acute pelvic pain, dysuria, and irritative voiding. Empiric UTI management with antimicrobials is complicated by increasing antimicrobial resistance among uropathogens, but live biotherapeutics products (LBPs), such as asymptomatic bacteriuria (ASB) strains of E. coli, offer the potential to circumvent antimicrobial resistance. Here we evaluated ASB E. coli as LBPs, relative to ciprofloxacin, for efficacy against infection and visceral pain in a murine UTI model. Visceral pain was quantified as tactile allodynia of the pelvic region in response to mechanical stimulation with von Frey filaments. Whereas ciprofloxacin promoted clearance of uropathogenic E. coli (UPEC), it did not reduce pelvic tactile allodynia, a measure of visceral pain. In contrast, ASB E. coli administered intravesically or intravaginally provided comparable reduction of allodynia similar to intravesical lidocaine. Moreover, ASB E. coli were similarly effective against UTI allodynia induced by Proteus mirabilis, Enterococccus faecalis and Klebsiella pneumoniae. Therefore, ASB E. coli have anti-infective activity comparable to the current standard of care yet also provide superior analgesia. These studies suggest that ASB E. coli represent novel LBPs for UTI symptoms.
The etiology of urinary tract infection: traditional and emerging pathogens
The American Journal of Medicine, 2002
The microbial etiology of urinary infections has been regarded as well established and reasonably consistent. Escherichia coli remains the predominant uropathogen (80%) isolated in acute community-acquired uncomplicated infections, followed by Staphylococcus saprophyticus (10% to 15%). Klebsiella, Enterobacter, and Proteus species, and enterococci infrequently cause uncomplicated cystitis and pyelonephritis. The pathogens traditionally associated with UTI are changing many of their features, particularly because of antimicrobial resistance. The etiology of UTI is also affected by underlying host factors that complicate UTI, such as age, diabetes, spinal cord injury, or catheterization. Consequently, complicated UTI has a more diverse etiology than uncomplicated UTI, and organisms that rarely cause disease in healthy patients can cause significant disease in hosts with anatomic, metabolic, or immunologic underlying disease. The majority of community-acquired symptomatic UTIs in elderly women are caused by E coli. However, gram-positive organisms are common, and polymicrobial infections account for up to 1 in 3 infections in the elderly. In comparison, the most common organisms isolated in children with uncomplicated UTI are Enterobacteriaceae. Etiologic pathogens associated with UTI among patients with diabetes include Klebsiella spp., Group B streptococci, and Enterococcus spp., as well as E coli. Patients with spinal cord injuries commonly have E coli infections. Other common uropathogens include Pseudomonas and Proteus mirabilis. Recent advances in molecular biology may facilitate the identification of new etiologic agents for UTI. The need for accurate and updated population surveillance data is apparent, particularly in light of concerns regarding antimicrobial resistance. This information will directly affect selection of empiric therapy for UTI.
International Journal of Infectious Diseases, 2013
Background: Escherichia coli is the predominant pathogen causing urinary tract infection (UTI), the most common bacterial infectious disease encountered in clinical practice, accounting for significant morbidity and high medical costs. The severity of UTI produced by E. coli is due to the expression of a wide spectrum of virulence factors. In this study we evaluated the role of E. coli virulence determinants in the pathogenesis of UTI. Methods: A total of 90 uropathogenic E. coli strains were screened by PCR for the prevalence of seven virulence genes encoding type 1 fimbriae (fimH), pili associated with pyelonephritis (pap), S and F1C fimbriae (sfa and foc), afimbrial adhesins (afa), cytotoxic necrotizing factor (cnf), hemolysin (hly), and aerobactin (aer). Results: The prevalence of genes coding for fimbrial adhesive systems was 68% for fimH, 41% for pap, and 34% for sfa/foc. The operons coding for afa afimbrial adhesins were identified in 20% of strains. The hly and cnf genes coding for toxins were amplified in 19% and 3% of strains, respectively. A prevalence of 52% was found for the aer gene. The various combinations of detected genes were designated as virulence patterns. The strains isolated from hospitalized patients displayed a great diversity of gene associations compared to those isolated from ambulatory patients. Conclusions: Our study showed that investigation of the bacterial pathogenicity associated with UTI may contribute to a better medical intervention.
The Journal of Urology, 1998
We evaluated the influence of urodynamic factors on the establishment of bacteriuria, after deliberate intravesical inoculation with Escherichia coli. 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. 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. 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.
Major trends in the microbial etiology of urinary tract infection
2019
Urinary tract infection (UTI) diagnosis is suggested by clinical findings (dysuria, pollakiuria) and confirmed by microbiological analysis of urine. Upon detection of pathogenic agents in the urine, antibiotic susceptibility testing (AST) should precede targeted antibiotic treatment. The growing prevalence of multiple resistant strains is a factor that poses serious challenges to antimicrobial therapy. Purpose: The aim of the study is to evaluate microbial resistance in patients with UTI’s at the St. Parascheva Infectious Disease Hospital in Iasi, Romania. Results: Frequently occurring infectious agents in the lot included gram negative bacteria (GNB), Enterococcus sp. and Candida sp. A percent of 37.8 % of strains were beta-lactamase releasing. The authors also noted increased gram negative bacteria resistance to beta-lactams. Conclusions: The bacteria isolated in decreasing order by frequency were: Escherichia coli, Pseudomonas, Enterococcusand Enterobacter. In order to avoid the ...