Search

There is currently a lack of experimental evidence for horizontal gene transfer (HGT) mechanisms in the human gut microbiota. The aim of this study was therefore to experimentally determine the HGT potential in the microbiota of a healthy preterm infant twin pair and to evaluate the global occurrence of the mobilized elements.

Amyloid deposits regress when the supply of fibril precursor proteins is sufficiently reduced, indicating that amyloid fibrils are degradable in vim. Serum amyloid P component (SAP), a universal constituent of amyloid deposits, efficiently protects amyloid fibrils from proteolysis in vitro, and may contribute to persistence of amyloid in vivo. Drugs that prevent binding of SAP to amyloid fibrils in vivo should therefore promote regression of amyloid and we are actively seeking such agents. A complementary strategy is identification of critical molecular processes in fibrillogenesis as targets for pharmacological intervention. All amyloidogenic variants of apolipoprotein AI contain an additional positive charge in the N-terminal fibrillogenic region of the protein. This is unlikely to be a coincidence and should be informative about amyloidogenesis by this protein. The two amyloidogenic variants of human lysozyme, caused by the first natural mutations found in its gene, provide a particularly powerful model system because both the crystal structure and folding pathways of wild-type lysozyme are so well characterized. The amyloidogenic variant lysozymes have similar 3D crystal structures to the wild type, but are notably less thermostable. They unfold on heating, lose enzymic activity, and aggregate to form amyloid fibrils in vitro.

α-Synuclein is a pre-synaptic protein, the function of which is not completely understood, but its pathological form is involved in neurodegenerative diseases. In vitro, α-synuclein spontaneously forms amyloid fibrils. Here, we report that αB-crystallin, a molecular chaperone found in Lewy bodies that are characteristic of Parkinson's disease (PD), is a potent in vitro inhibitor of α-synuclein fibrillization, both of wild-type and the two mutant forms (A30P and A53T) that cause familial, early onset PD. In doing so, large irregular aggregates of α-synuclein and αB-crystallin are formed implying that αB-crystallin redirects α-synuclein from a fibril-formation pathway towards an amorphous aggregation pathway, thus reducing the amount of physiologically stable amyloid deposits in favor of easily degradable amorphous aggregates. α-Synuclein acts as a molecular chaperone to prevent the stress-induced, amorphous aggregation of target proteins. Compared to wild-type α-synuclein, both mutant forms have decreased chaperone activity in vitro against the aggregation of reduced insulin at 37°C and the thermally induced aggregation of βL-crystallin at 60°C. Wild-type α-synuclein abrogates the chaperone activity of αB-crystallin to prevent the precipitation of reduced insulin. Interaction between these two chaperones and formation of a complex are also indicated by NMR spectroscopy, size-exclusion chromatography and mass spectrometry. In summary, α-synuclein and αB-crystallin interact readily with each other and affect each other's properties, in particular α-synuclein fibril formation and αB-crystallin chaperone action. © 2004 Elsevier Ltd. All rights reserved.

This study was conducted to elucidate the accuracy of the current streptomycin epidemiological cut-off value (ECOFF) for Escherichia coli and Salmonella spp. A total of 236 Salmonella enterica and 208 E. coli isolates exhibiting MICs between 4 and 32¿mg/L were selected from 12 countries. Isolates were investigated by polymerase chain reaction for aadA, strA, and strB streptomycin resistance genes. Out of 236 Salmonella isolates, 32 (13.5%) yielded amplicons for aadA (n¿=¿23), strA (n¿=¿9), and strB (n¿=¿11). None of the 60 Salmonella isolates exhibiting MIC 4¿mg/L harbored resistance genes. Of the Salmonella isolates exhibiting MICs 8¿mg/L, 16¿mg/L, and 32¿mg/L, 1.6%, 15%, and 39%, respectively, tested positive for one or more genes. For most monitoring programs, the streptomycin ECOFF for Salmonella is wild type (WT) =32 or =16¿mg/L. A cut-off value of WT =32¿mg/L would have misclassified 13.5% of the strains as belonging to the WT population, since this proportion of strains harbored resistance genes and exhibited MICs =32¿mg/L. Out of 208 E. coli strains, 80 (38.5%) tested positive for aadA (n¿=¿69), strA (n¿=¿18), and strB (n¿=¿31). Of the E. coli isolates exhibiting MICs of 4¿mg/L, 8¿mg/L, 16¿mg/L, and 32¿mg/L, 3.6%, 17.6%, 53%, and 82.3%, respectively, harbored any of the three genes. Based on the European Committee on Antimicrobial Susceptibility Testing guidelines (ECOFF =16¿mg/L), 25% of the E. coli strains presenting MIC =16¿mg/L would have been incorrectly categorized as belonging to the WT population. The authors recommend an ECOFF value of WT =16¿mg/L for Salmonella and WT =8¿mg/L for E. coli.

Objectives This study was initiated to collect retrospective information on the occurrence of plasmid-mediated quinolone resistance (PMQR) in Salmonella enterica and Escherichia coli isolates in Europe and to identify the responsible genes. Methods Databases of national reference laboratories containing MIC values for Salmonella and E. coli isolated between 1994 and 2009 in animals, humans, food and the environment from 13 European countries were screened for isolates exhibiting a defined quinolone resistance phenotype, i.e. reduced susceptibility to fluoroquinolones and nalidixic acid. PCR and sequence analysis were performed to identify the responsible PMQR genes. Results Screening of databases of 13 European countries resulted in a selection of 1215 Salmonella and 333 E. coli isolates. PMQR genes were identified in 59% of the Salmonella isolates and 15% of the E. coli isolates selected. In Salmonella, qnrS1 (n = 125) and variants of qnrB (n = 138) were frequently identified, whereas qnrA1 (n = 3) and aac(6′)-1b-cr (n = 3) were rarely found. qnrD was detected in 22 Salmonella isolates obtained from humans and animals. In E. coli, qnrS1 was identified in 19 isolates and qnrB19 was found in one isolate. No qnrC or qepA genes were detected in either Salmonella or E. coli. Conclusions This study shows the occurrence and dissemination of PMQR genes in Salmonella and E. coli in Europe with a defined quinolone resistance phenotype. We also report the first detection of qnrD in Salmonella collected in Europe.

Background: Risk factors that are associated with HIV infection are also associated with HBV and HCV infections in sub-Saharan Africa. The HIV-infected pregnant cohort represents a unique population and infection with the hepatitis virus is considered a public health problem worldwide. Objective: The purpose of this study was to evaluate the prevalence of Human Immunodeficiency Virus, Hepatitis B and C virus parallel and overlapping infections among pregnant women attending antenatal clinics in Federal Capital Territory (FCT), Abuja. Method: Five hundred (500) blood samples were collected from three district hospitals in the FCT and tested at Wuse General Hospital, Abuja for the presence of antibodies to HIV and Hepatitis C virus, and HBsAg by ELISA technique in accordance with the manufacturer’s instructions. HIV seropositive sera were confirmed by Western blot. Result: Of the 500 pregnant women, those detected with HIV antibodies, HBsAg and anti-HCV antibodies were 42 (8.4%), 19 (3.8%) and 8 (1.6%) respectively. The overall seroprevalence of HIV and HBV or HCV co-infection was 9.5% while 7.1% and 2.4% HIV positive pregnant women were specifically co-infected with HBV and HCV respectively. Those within the age bracket of 15-20 years had the highest prevalence of HIV (13.4%), HBV (5.1%) and HCV (1.9%) infections. Among the occupation characteristics of the women, those of them involved in trading recorded the highest prevalence of HIV (60.6%), HBV (30.3) and HCV (6.1%). HIV was higher among the married women than the singles ((8.6% vs 6.5%); with HBV infection the reverse was the case (3.0% vs 9.8%) while HCV was same for both groups. History of blood transfusion did not reflect a higher rate of HIV and HBV (1.4% vs 9.6%; 2.8% vs 4.0% respectively) unlike HCV infection with 0.5% recorded only among those that had transfusion experience. Conclusion: When monitoring the risk of hepatotoxicity to antiretroviral drugs among these group of patients caution should be maintained. Moreover, evidence of parallel and overlapping HIV, HBsAg and HCV infections among this cohort should motivate inclusion of HBV and HCV among the diseases of surveillance in the national sentinel survey in order to ascertain the bigger picture of these infections in Nigeria.

Microbiological and biochemical analyses of 59 breast nipple swab samples and 15 manually expressed breast milk samples of lactating mothers aged 15 to 40 years, was carried out using standard procedures. The incidence of bacterial species in swab samples was Staphylococus aureus (63.8%), Streptococcus sp (25.5%), Escherichia coli (6.4%) and Klebsiella sp (4.26%), indicating the poor sanitary status of the lactating mothers. S. aureus was recovered from only 1 (6.7%) of the milk samples, indicating that breast milk is relatively sterile. The nutritional values for the breast milk were 22.5 mg/ml (protein), 0.3 mg/ml (calcium), 3.5 mg/ml (sugar) and 300 microg/ml (vitamin A) in age group 15-20 years, and 16.4 mg/ml (protein), 0.16 mg/ml (calcium), 1.8 mg/ml (sugar) and 100 microg/ml (vitamin A) in the age group 36-40 years. In conclusion, the nutritive and antimicrobial properties of breast milk decrease with increasing age of lactating mothers. The need for public health enlightenment of lactating mothers regarding hygiene, and the provision of oral vitamin A supplement to infants, is discussed.