Helicobacter pylori Induces Inflammation in Mouse Urinary Bladder and Pelvis

Helicobacter pylori was transurethrally inoculated into the mouse urinary tract. The organism established infection and induced inflammation in the urinary bladder and pelvis. During the infection, urinary pH was elevated, probably due to the production of NH3 by bacterial urease. H. pylori was recovered from the urinary bladder, kidney and urine of the infected mice. Histopathologically, severe neutrophil infiltration was observed in the mucosal layer of both organs. H. pylori was detected on the surface of the epithelial cells. These results indicate that low pH and bacterial flora were not essential factors in establishing the mucosal infection with H. pylori. This experimental system is useful to investigate the pathogenicity of H. pylori in mucosal organs.     

Local and diffuse bacterial adherence on uroepithelial cells

The concept of local and diffuse adherence has been described for enteropathogenicEscherichia coli. In the present study, similar findings are reported for bacterial adherence to uroepithelial cells from patients with acute urinary tract infection and following incubation in an in vitro adherence assay. A population of cells were seen with few or no bacteria attached; others had localized areas of adherent organisms, while some cells were heavily colonized in a diffuse manner. These patterns were noted in vitro for anEscherichia coli strain and aLactobacillus casei strain, which possess different adhesins, therefore indicating that the adherence patterns were probably due to epithelial cell differences. The light microscopy and scanning electron microscopy observations illustrate that bacterial adherence to uroepithelial cells occurs in localized and diffuse distributions. The results indicate that there are differences in uroepithelial cell receptivity for bacterial attachment. The availability of cells receptive to uropathogens and indigenous flora, such as lactobacilli, is probably one of several factors that influence the pathogenesis of urinary tract infections.     

Iron dictates the virulence of <Emphasis Type="Italic">Pseudomonas aeruginosa</Emphasis> in urinary tract infections

Iron-limiting conditions have been reported to be prevalent in the milieu of urinary tract. In the present investigation, effect of iron on virulence of uropathogenic Pseudomonas aeruginosa in planktonic and biofilm cell mode was studied. Significant enhancement in elaboration of all the virulence traits along with increased adherence to uroepithelial cells and decreased phagocytosis of P. aeruginosa was observed following growth in iron-deplete medium. On the contrary, decrease in all these parameters except phagocytosis was observed when P. aeruginosa was grown in iron-rich medium. In vivo, P. aeruginosa grown in iron-deplete medium showed increased renal bacterial load and tissue pathology in a mouse model of ascending urinary tract infection compared with organisms grown in iron-replete medium. The results of the present study may help in understanding host–parasite interaction and in developing alternative preventive approach against P. aeruginosa induced urinary tract infections.     

Bactofection with Toll-Like Receptor 4 in a Murine Model of Urinary Tract Infection

The role of innate immunity in the prevention of urinary tract infection is well-documented. Toll-like receptor 4 (TLR4) is a major determinant of innate immune response. In an animal model of urinary tract infection, bactofection-mediated gene transfer of TLR4 was tested in a preventive approach. Bactofection with TLR4 reduced the colonization with uropathogenic Escherichia coli by 91% in the kidney and by 41% in the bladder. Reduced colonization was associated with lower oxidative stress and expression of monocyte chemoattractant protein-1 and myeloperoxidase in the kidney. Bactofection with TLR4 was successful in the prevention of ascending pyelonephritis. Further studies should focus on long-term effects, the dose response and the potential therapeutic use in models of chronic urinary tract infection.     

Case-control study of self reported genitourinary infections and risk of gastroschisis: findings from the national birth defects prevention study, 1997-2003

Objective To assess the association between genitourinary infections in the month before conception to the end of the first trimesterand gastroschisis.Design Case-control study with self reported infections from a computer assisted telephone interview.Setting National birth defects prevention study, a multisite, population based study including 10 surveillance systems for birth defects in the United States.Participants Mothers of 505 offspring with gastroschisis and 4924 healthy liveborn infants as controls.Main outcome measure Adjusted odds ratios for gastroschisis with 95% confidence intervals.Results About 16% (n=81) of case mothers and 9% (n=425) of control mothers reported a genitourinary infection in the relevant time period; 4% (n=21) and 2% (n=98) reported a sexually transmitted infection and 13% (n=67) and 7% (n=338) reported a urinary tract infection, respectively. Case mothers aged <25 years reported higher rates of urinary tract infection alone and in combination with a sexually transmitted infection compared with control mothers. In women who reported both types of infection, there was a greater risk of gastroschisis in offspring (adjusted odds ratio 4.0, 95% confidence interval 1.4 to 11.6).Conclusion There is a significant association between self reported urinary tract infection plus sexually transmitted infection just before conception and in early pregnancy and gastroschisis.     

肠道与泌尿系统的微生物对肾结石发病机制影响的研究进展

肾结石是成人泌尿系统的常见疾病。它会影响肾脏的生理机能,还会导致尿路感染从而对人体健康造成一定危害。肾结石周围存在一个多元化的微生物群落,而肠道微生物和泌尿系统微生物的变化可能引起肾结石的发生与发展。其中双歧杆菌(Bifidobacterium)、乳酸杆菌(Lactobacillus)和肠杆菌科(Enterobacteriaceae)与肾结石发生较为密切。本篇综述着重介绍了肠道微生物与泌尿系统微生物在肾结石形成过程中的关联性,同时也对肾-肠轴概念,肠道微生物从短链脂肪酸产生、草酸盐变化和炎症发生对肾结石的影响,以及肾结石的预防与治疗等方面做出了介绍。     

Proteomic analysis of uropathogenic Escherichia coli

Urinary tract infections (UTIs) are among the most common of bacterial infections in humans. Although a number of Gram-negative bacteria can cause UTIs, most cases are due to infection by uropathogenic E. coli (UPEC). Genomic studies have shown that UPEC encode a number of specialized activities that allow the bacteria to initiate and maintain infections in the environment of the urinary tract. Proteomic analyses have complemented the genomic data and have documented differential patterns of protein synthesis for bacteria growing ex vivo in human urine or recovered directly from the urinary tracts of infected mice. These studies provide valuable insights into the molecular basis of UPEC pathogenesis and have aided the identification of putative vaccine targets. Despite the substantial progress that has been achieved, many future challenges remain in the application of proteomics to provide a comprehensive view of bacterial pathogenesis in both acute and chronic UTIs.     

Chromosomal and plasmid encoded drug resistances of a <Emphasis Type="Italic">Klebsiella pneumoniae</Emphasis> UTI 2 strain isolated from urine of a post-operative patient

The multi drug resistance Klebsiella pneumoniae in urinary tract infection is a common clinical problem in developing country like India. Use of random antibiotics, resulting multi drug resistance development, creates difficulties for treatment. In our present study, we investigated a strain of Klebsiella pneumoniae UTI 2 with multiple drug resistance, which was isolated from urine of a post operative woman patient (50 years) suffering from urinary tract infection with high fever. This strain is resistant to 36 antibiotics and sensitive to cefotaxime (Ce) and imipenem (I). After curing of plasmids, we observed that, 55% of drug resistant loci of K. pneumoniae UTI 2 are chromosomal and 40% are plasmid encoded. The organism is sensitive to 5% of drugs tested, i.e. Ce and I. This study contributes to understand the drug resistance of Klebsiella pneumoniae, which will enable better clinical management of catheter-associated urinary tract infections, a major health problem.     

Synergy between type 1 fimbriae expression and C3 opsonisation increases internalisation of E. coli by human tubular epithelial cells

Background  

Bacterial infection of the urinary tract is a common clinical problem with E. coli being the most common urinary pathogen. Bacterial uptake into epithelial cells is increasingly recognised as an important feature of infection. Bacterial virulence factors, especially fimbrial adhesins, have been conclusively shown to promote host cell invasion. Our recent study reported that C3 opsonisation markedly increases the ability of E. coli strain J96 to internalise into human proximal tubular epithelial cells via CD46, a complement regulatory protein expressed on host cell membrane. In this study, we further assessed whether C3-dependent internalisation by human tubular epithelial cells is a general feature of uropathogenic E. coli and investigated features of the bacterial phenotype that may account for any heterogeneity.     

RESISTANT URINARY TRACT INFECTIONS—Combined Autogenous Vaccine and Drug Therapy

The “miracle” antibiotics and sulfa drugs have been found unsatisfactory in treating certain severe resistant urinary tract infections apparently due to lack of immunity factor in the patient. Of a series of 56 patients with resistant urinary tract infection who were treated with autogenous vaccine and then with sulfa drugs, 26 were completely cured.     

dsdA Does Not Affect Colonization of the Murine Urinary Tract by Escherichia coli CFT073

The urinary tract environment provides many conditions that deter colonization by microorganisms. D-serine is thought to be one of these stressors and is present at high concentrations in urine. D-serine interferes with L-serine and pantothenate metabolism and is bacteriostatic to many species. Uropathogenic Escherichia coli commonly possess the dsdCXA genetic locus, which allows them to use D-serine as a sole carbon, nitrogen, and energy source. It was previously reported that in the model UPEC strain CFT073, a dsdA mutant outcompetes wild type in the murine model of urinary tract infection. This “hypercolonization” was used to propose a model whereby UPEC strains sense D-serine in the urinary tract and subsequently up-regulate genes necessary for pathogenesis. Here, we show that inactivation of dsdA does not lead to hypercolonization. We suggest that this previously observed effect is due to an unrecognized secondary mutation in rpoS and that some D-serine specific effects described in other studies may be affected by the rpoS status of the strains used. Inactivation of dsdA in the original clinical isolate of CFT073 gives CFT073 ΔdsdA a growth defect in human urine and renders it unable to grow on minimal medium containing D-serine as the sole carbon source. However, CFT073 ΔdsdA is able to colonize the urinary tracts of CBA/J mice indistinguishably from wild type. These findings indicate that D-serine catabolism, though it may play role(s) during urinary tract infection, does not affect the ability of uropathogenic E. coli to colonize the murine urinary tract.     

Epidemiology of urinary tract diseases in general practice

During a one-year morbidity survey of urinary tract diseases in general practice 741 cases were diagnosed. Only about half of all the patients with symptoms of urinary tract infection had significant bacteriuria. In young women urinary tract infections and symptoms from the urinary tract without bacteriuria—in particular urethritis—were found to predominate. In middle-aged women, the urinary tract symptoms were ascribed increasingly to genital prolapse, while incidence of urolithiasis was the highest in any group, and urinary tract infections became less frequent. The prevalence of urinary tract infection showed another increase in elderly women, and recurrent/chronic pyelonephritis, which occurs with a steadily increasing prevalence throughout all age groups, became common.In younger male urological patients diseases with symptoms of urinary tract infection without bacteriuria were predominant, whereas prostatitis and urinary tract infections were less frequent. In middle-aged men, urolithiasis was especially frequent, while an increasing proportion of elderly men had prostatic hypertrophy, urinary tract infections, and recurrent/chronic pyelonephritis.     

Struvite calculus in the vagina of a bottlenose dolphin (Tursiops truncatus)

On 27 January 2000, a struvite calculus was observed in the vagina during necropsy of a 138-cm-long female bottlenose dolphin (Tursiops truncatus) collected from the Stono River, South Carolina (USA). Vaginal calculi have been reported in other species of cetaceans but not in bottlenose dolphins. Urinary tract infection might have been an underlying cause of the calculus. While urinary tract inflammation was not detected by light microscopic evaluation of sections of the urinary tract, it is conceivable that sufficient time had lapsed following voiding of the calculus through the urethra for urinary tract infection to have resolved. To further define the prevalence and significance of urolithiasis, prosectors of dead stranded marine mammals are encouraged to closely observe their urinary and genital tracts for calculi and to submit them for quantitative analysis.     

Community behavior and amyloid-associated phenotypes among a panel of uropathogenic E. coli

Uropathogenic Escherichia coli (UPEC) are the major causative agents of urinary tract infection and engage in a coordinated genetic and molecular cascade to colonize the urinary tract. Disrupting the assembly and/or function of virulence factors and bacterial biofilms has emerged as an attractive target for the development of new therapeutic strategies to prevent and treat urinary tract infection, particularly in the era of increasing antibiotic resistance among human pathogens. UPEC vary widely in their genetic and molecular phenotypes and more data are needed to understand the features that distinguish isolates as more or less virulent and as more robust biofilm formers or poor biofilm formers. Curli are extracellular functional amyloid fibers produced by E. coli that contribute to pathogenesis and influence the host response during urinary tract infection (UTI). We have examined the production of curli and curli-associated phenotypes including biofilm formation among a specific panel of human clinical UPEC that has been studied extensively in the mouse model of UTI. Motility, curli production, and curli-associated biofilm formation attached to plastic were the most prevalent behaviors, shared by most clinical isolates. We discuss these results in the context on the previously reported behavior and phenotypes of these isolates in the murine cystitis model in vivo.     

Preventive and therapeutic administration of an indigenous <Emphasis Type="Italic">Lactobacillus</Emphasis> sp. strain against <Emphasis Type="Italic">Proteus mirabilis</Emphasis> ascending urinary tract infection in a mouse model

Probiotics are increasingly being considered as non-pharmaceutical and safe potential alternatives for the treatment and prevention of a variety of pathologies including urinary tract infections. These are the most common infections in medical practice and are frequently treated with antibiotics, which have generated an intense selective pressure over bacterial populations. Proteus mirabilis is a common cause of urinary tract infections in catheterised patients and people with abnormalities of the urinary tract. In this work we isolated, identified and characterised an indigenous Lactobacillus murinus strain (LbO2) from the vaginal tract of a female mouse. In vitro characterisation of LbO2 included acid and bile salts tolerance, growth in urine, adherence to uroepithelial cells and in vitro antimicrobial activity. The selected strain showed interesting properties, suitable for its use as a probiotic. The ability of LbO2 to prevent and even treat ascending P. mirabilis urinary tract infection was assessed using an experimental model in the mouse. Kidney and bladder P. mirabilis counts were significantly lower in mice preventively treated with the probiotic than in non-treated mice. When LbO2 was used for therapeutic treatment, bladder counts of treated mice were significantly lower although no significant differences were detected in P. mirabilis kidney colonisation of treated and non-treated animals. These results are encouraging and prompt further research related to probiotic strains and the basis of their effects for their use in human and animal health.     

Susceptibility of Pseudomonas aeruginosa Urinary Tract Isolates and Influence of Urinary Tract Conditions on Antibiotic Tolerance

Pseudomonas aeruginosa is an opportunistic human pathogen, which can cause severe urinary tract infections (UTIs). Because of the high intrinsic antibiotic resistance of P. aeruginosa and its ability to develop new resistances during antibiotic treatment, these infections are difficult to eradicate. The antibiotic susceptibility of 32 P. aeruginosa isolates from acute and chronic UTIs were analysed under standardized conditions showing 19% multi-drug resistant strains. Furthermore, the antibiotic tolerance of two P. aeruginosa strains to ciprofloxacin and tobramycin was analysed under urinary tract-relevant conditions which considered nutrient composition, biofilm growth, growth phase, and oxygen concentration. These conditions significantly enhance the antibiotic tolerance of P. aeruginosa up to 6000-fold indicating an adaptation of the bacterium to the specific conditions present in the urinary tract. This reversible phenomenon is possibly due to the increased formation of persister cells and is based on iron limitation in artificial urine. The results suggest that the general high antibiotic resistance of P. aeruginosa urinary tract isolates together with the increasing tolerance of P. aeruginosa grown under urinary tract conditions decrease the efficiency of antibiotic treatment of UTIs.     

Resistant urinary tract infections; combined autogenous vaccine and drug therapy

The "miracle" antibiotics and sulfa drugs have been found unsatisfactory in treating certain severe resistant urinary tract infections apparently due to lack of immunity factor in the patient. Of a series of 56 patients with resistant urinary tract infection who were treated with autogenous vaccine and then with sulfa drugs, 26 were completely cured.     

Therapeutic experience with netilmicin.

Netilmicin, a new aminoglycoside antibiotic, was used to treat 19 patients with urinary tract infection and 5 with systemic infection. The causal organisms were Escherichia coli (in 2), Klebsiella pneumoniae (in 4), Serratia marcescens (in 12) and Pseudomonas aeruginosa (in 7); 1 patient was infected with two of these organisms. All the isolates of causal organisms except one of Serratia were initially sensitive to netilmicin but many were resistant to other aminoglycosides. Sixteen of the urinary tract infections responded to netilmicin therapy, although relapse occurred in three patients. Two of the three patients with musculoskeletal infection responded to combined therapy with surgery and netilmicin; the other patient responded to the same regimen but with carbenicillin added. Netilmicin cured pneumonia in one patient but failed in the other patient with pneumonia, who had leukemia. Superinfection occurred in five patients with urinary tract infection. Adverse reactions to netilmicin were minor. Netilmicin may prove to be a useful agent, particularly for infections due to multiresistant Klebsiella or Serratia, or when prolonged aminoglycoside therapy is required.