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Concept: Urease


We describe a novel infection-responsive coating for urinary catheters that provides a clear visual early warning of Proteus mirabilis infection and subsequent blockage. The crystalline biofilms of P. mirabilis can cause serious complications for patients undergoing long-term bladder catheterisation. Healthy urine is around pH 6, bacterial urease increases urine pH leading to the precipitation of calcium and magnesium deposits from the urine, resulting in dense crystalline biofilms on the catheter surface that blocks urine flow. The coating is a dual layered system in which the lower poly(vinyl alcohol) layer contains the self-quenching dye carboxyfluorescein. This is capped by an upper layer of the pH responsive polymer poly(methyl methacrylate-co-methacrylic acid) (Eudragit S100®). Elevation of urinary pH (>pH 7) dissolves the Eudragit layer, releasing the dye to provide a clear visual warning of impending blockage. Evaluation of prototype coatings using a clinically relevant in vitro bladder model system demonstrated that coatings provide up to 12h advanced warning of blockage, and are stable both in the absence of infection, and in the presence of species that do not cause catheter blockage. At the present time, there are no effective methods to control these infections or provide warning of impending catheter blockage.

Concepts: Present, Time, Bacteria, Urine, Urinary system, Urease, Urinary catheterization, Proteus mirabilis


The epidemiology of Helicobacter pylori infection has changed with improvements in sanitation and methods of eradication. We performed a systematic review and meta-analysis to evaluate changes in the global prevalence of H pylori infection.

Concepts: Gastroenterology, Helicobacter pylori, Helicobacter, Urease


The bacterium Helicobacter pylori (H. pylori), has evolved to survive in the highly acidic environment of the stomach and colonize on the epithelial surface of the gastric mucosa. Its pathogenic effects are well known to cause gastritis, peptic ulcers, and gastric cancer. In order to infect the stomach and establish colonies on the mucus epithelial surface, the bacterium has to move across the gel-like gastric mucus lining of the stomach under acidic conditions. In this review we address the question of how the bacterium gets past the protective mucus barrier from a biophysical perspective. We begin by reviewing the molecular structure of gastric mucin and discuss the current state of understanding concerning mucin polymerization and low pH induced gelation. We then focus on the viscoelasticity of mucin in view of its relevance to the transport of particles and bacteria across mucus, the key first step in H. pylori infection. The second part of the review focuses on the motility of H. pylori in mucin solutions and gels, and how infection with H. pylori in turn impacts the viscoelastic properties of mucin. We present recent microscopic results tracking the motion of H. pylori in mucin solutions and gels. We then discuss how the biochemical strategy of urea hydrolysis required for survival in the acid is also relevant to the mechanism that enables flagella-driven swimming across the mucus gel layer. Other aspects of the influence of H. pylori infection such as, altering gastric mucin expression, its rate of production and its composition, and the influence of mucin on factors controlling H. pylori virulence and proliferation are briefly discussed with references to relevant literature.

Concepts: Bacteria, Gastroenterology, Stomach, Helicobacter pylori, Peptic ulcer, Helicobacter, Urease, Gastritis


ETHNOPHARMACOLOGICAL RELEVANCE: Glycyrrhiza glabra Linn. is regarded useful for peptic ulcer in traditional systems of medicine in India. AIM OF THE STUDY: Helicobacter pylori has been considered as one of the causative factors for peptic ulcer. Aim of the present study was to evaluate the anti-H. pylori action of GutGard(®), a flavonoid rich extract of G. glabra and further to elucidate the possible mechanisms of its anti-H. pylori action. MATERIALS AND METHODS: Agar dilution and microbroth dilution methods were used to determine the minimum inhibitory concentration of GutGard(®) against H. pylori. Protein synthesis, DNA gyrase, dihydrofolate reductase assays and anti-adhesion assay in human gastric mucosal cell line were performed to understand the mechanisms of anti-H. pylori activity of GutGard(®). RESULTS: GutGard(®) exhibited anti-H. pylori activity in both agar dilution and microbroth dilution methods. Glabridin, the major flavonoid present in GutGard(®) exhibited superior activity against H. pylori while glycyrrhizin did not show activity even at 250µg/ml concentration. In protein synthesis assay, GutGard(®) showed a significant time dependent inhibition as witnessed by the reduction in (35)S methionine incorporation into H. pylori ATCC 700392 strain. Additionally, GutGard(®) showed a potent inhibitory effect on DNA gyrase and dihydrofolate reductase with IC(50) value of 4.40μg/ml and 3.33μg/ml respectively. However, the extract did not show significant inhibition on the adhesion of H. pylori to human gastric mucosal cell line at the tested concentrations. CONCLUSION: The present study shows that, GutGard(®) acts against H. pylori possibly by inhibiting protein synthesis, DNA gyrase and dihydrofolate reductase.

Concepts: DNA, Bacteria, Gastroenterology, Stomach, Helicobacter pylori, Peptic ulcer, Helicobacter, Urease


Objective: An association between Helicobacter pylori (H. pylori) and thrombocytopenia has been demonstrated in the literature in a non-pregnant population. The purpose of this study was to determine whether or not there is a similar association in the third trimester of pregnancy in a Hispanic population. Methods: This is a secondary analysis of 82 pregnant Hispanic women with and without hyperemesis gravidarum who underwent serologic evaluation for H. pylori IgG. Results of complete blood counts obtained in the third trimester were analysed for thrombocytopenia. Results: Of the 82 subjects who had H. pylori testing, 54 subjects had both serum H. pylori IgG results and third trimester platelet levels. The prevalence of thrombocytopenia was 11.1% (6/54). Thirty-six subjects were seropositive for H. pylori IgG and 18 subjects were seronegative. Of the 36 subjects who were H. pylori seropositive, four (11.1%) developed thrombocytopenia compared to three of 18 (16.7%) H. pylori seronegative subjects (P = 0.67). There was no difference between the groups in their mean platelet values (205 K/cu mm vs. 212 K/cu mm, P = 0.69). Conclusions: In this limited study, we found no association between H. pylori and thrombocytopenia in the pregnant Hispanic population.

Concepts: Pregnancy, Platelet, Gastroenterology, Helicobacter pylori, Helicobacter, Thrombocytopenia, Urease, Giulio Bizzozero


Proteus mirabilis is a common cause of urinary tract infection. Wild-type P. mirabilis strains are usually susceptible to penicillins and cephalosporins, but occurrences of P. mirabilis producing extended-spectrum β-lactamases (ESBLs) have been recently reported. Here, we surveyed the prevalence of cefotaxime resistance among P. mirabilis strains at seven different hospitals in Kanagawa Prefecture, Japan, and investigated their molecular epidemiology to explain the mechanism of their spread. The prevalence of cefotaxime resistance among P. mirabilis increased annually, from 10.1 % in 1998 to 23.1 % in 2003, and increased drastically in 2004, exceeding 40 %. We collected 105 consecutive and non-duplicate cefotaxime-resistant P. mirabilis isolates (MIC 16 to >256 µg ml(-1)) from these hospitals from June 2004 to May 2005 and characterized their profile. PCR and sequence analysis revealed that all resistant strains produced exclusively CTX-M-2 β-lactamase. PFGE analysis identified 47 banding patterns with 83 % or greater similarity. These results indicated that a regional outbreak of P. mirabilis producing CTX-M-2 β-lactamase has occurred in Japan and suggest that the epidemic spread occurred within and across hospitals and communities by extended clonal strains. Plasmid analysis revealed that 44.8 % of plasmids harboured by bla(CTX-M-2) isolates had common profiles, encoding ISEcp1, IS26 and Int1, and belonged to incompatibility group T. Spread of the resistant isolates in Japan resulted from dissemination of narrow-host-range plasmids of the IncT group encoding bla(CTX-M-2). These findings indicate the rapidly developing problem of treating the species to prevent dissemination of ESBL producers.

Concepts: Epidemiology, Urinary tract infection, Plasmid, Urease, Prefectures of Japan, Proteus mirabilis, Honshū, Kanagawa Prefecture


Eradication rates of Helicobacter pylori with standard triple therapy are not satisfactory. Sequential therapy is an alternative method to overcome this problem.

Concepts: Gastroenterology, Helicobacter pylori, Proteobacteria, Helicobacter, Urease


Proteus mirabilis, named for the Greek god who changed shape to avoid capture, has fascinated microbiologists for more than a century with its unique swarming differentiation, Dienes line formation and potent urease activity. Transcriptome profiling during both host infection and swarming motility, coupled with the availability of the complete genome sequence for P. mirabilis, has revealed the occurrence of interbacterial competition and killing through a type VI secretion system, and the reciprocal regulation of adhesion and motility, as well as the intimate connections between metabolism, swarming and virulence. This Review addresses some of the unique and recently described aspects of P. mirabilis biology and pathogenesis, and emphasizes the potential role of this bacterium in single-species and polymicrobial urinary tract infections.

Concepts: DNA, Bacteria, Microbiology, Virus, Genome, Urease, Proteus mirabilis, Swarming motility


Although Proteus mirabilis is a common human pathogen, bacteremia caused by the organism, especially strains producing extended-spectrum beta-lactamase (ESBL), has rarely been investigated. We examined 64 cases of P. mirabilis bacteremia identified in the Minami Ibaraki Area, Japan, between 2001 and 2010 and compared the characteristics of cases with ESBL-producing and ESBL-non-producing strains (13 and 51 cases, respectively). All ESBL-producing strains with the gene encoding the CTX-M-2-group were genetically nonidentical. Isolation of ESBL-producing strains was significantly associated with onset in a hospital (p = 0.030), receiving hemodialysis (p = 0.0050), and previous antibiotic use within 1 month (p = 0.036; especially penicillin and/or cephalosporin (p = 0.010) and fluoroquinolone (p = 0.0069)). Isolation was also associated with inappropriate antibiotic therapy on the 1st and 4th days (p = 0.011 and 0.032, respectively) but not with mortality on the 30th day. These findings indicate that, for P. mirabilis bacteremia, isolation of ESBL-producing strains causes delay of initiating appropriate antimicrobial therapy but may not be associated with mortality.

Concepts: Gene, Bacteria, Microbiology, Antibiotic, Urease, Penicillin, Beta-lactamase, Proteus mirabilis


To determine the most efficacious treatment for eradication of Helicobacter pylori with the lowest likelihood of some common adverse events among pre-recommended and newer treatment regimens.

Concepts: Effectiveness, Gastroenterology, Helicobacter pylori, Proteobacteria, Helicobacter, Meta-analysis, Urease