Comparative proteomics of uropathogenic Escherichia coli during growth in human urine identify UCA-like (UCL) fimbriae as an adherence factor involved in biofilm formation and binding to uroepithelial cells

Uropathogenic Escherichia coli (UPEC) are the primary cause of urinary tract infection (UTI) in humans. For the successful colonisation of the human urinary tract, UPEC employ a diverse collection of secreted or surface-exposed virulence factors including toxins, iron acquisition systems and adhesins. In this study, a comparative proteomic approach was utilised to define the UPEC pan and core surface proteome following growth in pooled human urine. Identified proteins were investigated for subcellular origin, prevalence and homology to characterised virulence factors. Fourteen core surface proteins were identified, as well as eleven iron uptake receptor proteins and four distinct fimbrial types, including type 1, P, F1C/S and a previously uncharacterised fimbrial type, designated UCA-like (UCL) fimbriae in this study. These pathogenicity island (PAI)-associated fimbriae are related to UCA fimbriae of Proteus mirabilis, associated with UPEC and exclusively found in members of the E. coli B2 and D phylogroup. We further demonstrated that UCL fimbriae promote significant biofilm formation on abiotic surfaces and mediate specific attachment to exfoliated human uroepithelial cells. Combined, this study has defined the surface proteomic profiles and core surface proteome of UPEC during growth in human urine and identified a new type of fimbriae that may contribute to UTI

Clozapine treatment in patients living in the community

OBJECTIVE: The aim of this study was to assess clozapine treatment in the local community with respect to patient monitoring during dispensing, patient compliance through prescription refills, presence of any other existing co-morbidities and presence of potential drug-drug interactions. METHOD: An audit on whether pharmacy personnel check patients’ white blood cell count and absolute neutrophil count prior to dispensing was performed. A total of 100 audits were carried out. A computer programme entitled ‘Pharmacy Dispensing System’ was used to assess patient compliance through prescription refills over a 3-month period. Another computer programme entitled ‘Schedule V’ was used to determine any other comorbidities. After determining the list of all the chronic medications, analysis of the presence of any potential drugdrug interactions was undertaken. The ‘Drug Interaction Checker’, a drug interaction database provided by RxList, was used. This database classified potential drug-drug interactions into 3 categories namely minor, significant and serious. KEY FINDINGS: The white blood cell count and absolute neutrophil count were checked in all instances (N=100), however this intervention was not documented. Over a 3-month period, 78 out of 90 patients were compliant. Diabetes was the most common co-morbidity (n=15) and 76 patients receiving clozapine may be exposed to a potential drug-drug interaction. A total of 363 possible drug interactions were present in this group of patients. The most common type of potential drug-drug interaction fell in the ‘significant drug-drug interactions’ category (n=289). CONCLUSION: Patient monitoring was carried out, however documentation processes need to be elaborated. Identification of drug interactions is of utmost importance since certain interactions can be dangerous. Apart from detecting drug interactions, discussion with other healthcare professionals should be undertaken to assess the possibility of replacing such interacting drugs with alternative options. This measure should be carried out to promote patient safety.peer-reviewe

Comparison of commercial diagnostic tests for Helicobacter pylori antibodies

A number of serological tests measuring the presence of Helicobacter pylori-specific serum immunoglobulin G (IgG) are now commercially available. The aim of this study was to evaluate the clinical accuracy of five commercial H. pylori antibody tests: GAP-IgG (Biomerica), HELpTEST (AMRAD, Kew, Victoria, Australia), HELICO-G (Porton Cambridge), Pyloriset (Orion Diagnostica), and ROCHE (Roche Diagnostics). A total of 162 subjects presenting for routine upper endoscopy were studied. H. pylori was diagnosed if culture, histology, or both were positive. Ten milliliters of venous blood was collected at the time of endoscopy for serological assessment. The sensitivity and specificity of each test (GAP-IgG, HELpTEST, HELICO-G, Pyloriset, and ROCHE) were as follows: 83 and 79%, 92 and 77%, 86 and 65%, 89 and 56%, and 98 and 69%, respectively. Positive and negative predictive values were 97 and 83%, 90 and 91%, 76 and 83%, 68 and 84%, and 86 and 97%, respectively. The specificity of most tests increased by approximately 10% when sera from subjects less than 45 years old were examined. The number of sera falling into the grey zone for each test (an indeterminate result with respect to H. pylori status) varied between 2.5 and 19%. This study highlights the need for all serological kits to be independently evaluated on the population to be studied by testing against a microbiologically defined panel of H. pylori-positive and -negative sera

Molecular epidemiology of multidrug-resistant Acinetobacter baumannii in a single institution over a 10-year period

The molecular epidemiology and mechanisms of resistance of carbapenem-resistant Acinetobacter baumannii (CRAB) were determined in hospitals in the states of the Cooperation Council for the Arab States of the Gulf (Gulf Cooperation Council [GCC]), namely, Saudi Arabia, United Arab Emirates, Oman, Qatar, Bahrain, and Kuwait. Isolates were subjected to PCR-based detection of antibiotic resistance genes and repetitive sequence-based PCR (rep-PCR) assessments of clonality. Selected isolates were subjected to multilocus sequence typing (MLST). We investigated 117 isolates resistant to carbapenem antibiotics (either imipenem or meropenem). All isolates were positive for OXA-51. The most common carbapenemases were the OXA-23-type, found in 107 isolates, followed by OXA-40-type (OXA-24-type), found in 5 isolates; 3 isolates carried the ISAba1 element upstream of blaOXA-51-type. No OXA-58-type, NDM-type, VIM-type, or IMP-type producers were detected. Multiple clones were detected with 16 clusters of clonally related CRAB. Some clusters involved hospitals in different states. MLST analysis of 15 representative isolates from different clusters identified seven different sequence types (ST195, ST208, ST229, ST436, ST450, ST452, and ST499), as well as three novel STs. The vast majority (84%) of the isolates in this study were associated with health care exposure. Awareness of multidrug-resistant organisms in GCC states has important implications for optimizing infection control practices; establishing antimicrobial stewardship programs within hospital, community, and agricultural settings; and emphasizing the need for establishing regional active surveillance systems. This will help to control the spread of CRAB in the Middle East and in hospitals accommodating transferred patients from this region

Reduction in urinary organophosphate pesticide metabolites in adults after a week-long organic diet

Background Conventional food production commonly uses organophosphate (OP) pesticides, which can have negative health effects, while organic food is deemed healthier because it is produced without these pesticides. Studies suggest that organic food consumption may significantly reduce OP pesticide exposure in children who have relatively higher pesticide exposure than adults due to their different diets, body weight, behaviour and less efficient metabolism. Objectives A prospective, randomised, crossover study was conducted to determine if an organic food diet reduces organophosphate exposure in adults. Methods Thirteen participants were randomly allocated to consume a diet of at least 80% organic or conventional food for 7 days and then crossed over to the alternate diet. Urinary levels of six dialkylphosphate metabolites were analysed in first-morning voids collected on day 8 of each phase using GC-MS/MS with detection limits of 0.11-0.51 ug/L. Results The mean total DAP results in the organic phase were 89% lower than in the conventional phase (M=0.032 [SD=0.038] and 0.294 [SD=0.435] respectively, p=0.013). For total dimethyl DAPs there was a 96% reduction (M=0.011 [SD=0.023] and 0.252 [SD=0.403] respectively, p=0.005). Mean total diethyl DAP levels in the organic phase were half those of the conventional phase (M=0.021 [SD=0.020] and 0.042 [SD=0.038] respectively), yet the wide variability and small sample size meant the difference was not statistically significant. Conclusions The consumption of an organic diet for one week significantly reduced OP pesticide exposure in adults. Larger scale studies in different populations are required to confirm these findings and investigate their clinical relevance

Regulation of surface architecture by symbiotic bacteria mediates host colonization

Microbes occupy countless ecological niches in nature. Sometimes these environments may be on or within another organism, as is the case in both microbial infections and symbiosis of mammals. Unlike pathogens that establish opportunistic infections, hundreds of human commensal bacterial species establish a lifelong cohabitation with their hosts. Although many virulence factors of infectious bacteria have been described, the molecular mechanisms used during beneficial host–symbiont colonization remain almost entirely unknown. The novel identification of multiple surface polysaccharides in the important human symbiont Bacteroides fragilis raised the critical question of how these molecules contribute to commensalism. To understand the function of the bacterial capsule during symbiotic colonization of mammals, we generated B. fragilis strains deleted in the global regulator of polysaccharide expression and isolated mutants with defects in capsule expression. Surprisingly, attempts to completely eliminate capsule production are not tolerated by the microorganism, which displays growth deficits and subsequent reversion to express capsular polysaccharides. We identify an alternative pathway by which B. fragilis is able to reestablish capsule production and modulate expression of surface structures. Most importantly, mutants expressing single, defined surface polysaccharides are defective for intestinal colonization compared with bacteria expressing a complete polysaccharide repertoire. Restoring the expression of multiple capsular polysaccharides rescues the inability of mutants to compete for commensalism. These findings suggest a model whereby display of multiple capsular polysaccharides provides essential functions for bacterial colonization during host–symbiont mutualism