Cryptic prophages within a Streptococcus pyogenes genotype emm4 lineage

The major human pathogen Streptococcus pyogenes shares an intimate evolutionary history with mobile genetic elements, which in many cases carry genes encoding bacterial virulence factors. During recent whole-genome sequencing of a longitudinal sample of S. pyogenes isolates in England, we identified a lineage within emm4 that clustered with the reference genome MEW427. Like MEW427, this lineage was characterized by substantial gene loss within all three prophage regions, compared to MGAS10750 and isolates outside of the MEW427-like lineage. Gene loss primarily affected lysogeny, replicative and regulatory modules, and to a lesser and more variable extent, structural genes. Importantly, prophage-encoded superantigen and DNase genes were retained in all isolates. In isolates where the prophage elements were complete, like MGAS10750, they could be induced experimentally, but not in MEW427-like isolates with degraded prophages. We also found gene loss within the chromosomal island SpyCIM4 of MEW427-like isolates, although surprisingly, the SpyCIM4 element could not be experimentally induced in either MGAS10750-like or MEW427-like isolates. This did not, however, appear to abolish expression of the mismatch repair operon, within which this element resides. The inclusion of further emm4 genomes in our analyses ratified our observations and revealed an international emm4 lineage characterized by prophage degradation. Intriguingly, the USA population of emm4 S. pyogenes appeared to constitute predominantly MEW427-like isolates, whereas the UK population comprised both MEW427-like and MGAS10750-like isolates. The degraded and cryptic nature of these elements may have important phenotypic and fitness ramifications for emm4 S. pyogenes , and the geographical distribution of this lineage raises interesting questions on the population dynamics of the genotype

Activity and Interactions of Liposomal Antibiotics in Presence of Polyanions and Sputum of Patients with Cystic Fibrosis

BACKGROUND:To compare the effectiveness of liposomal tobramycin or polymyxin B against Pseudomonas aeruginosa in the Cystic Fibrosis (CF) sputum and its inhibition by common polyanionic components such as DNA, F-actin, lipopolysaccharides (LPS), and lipoteichoic acid (LTA). METHODOLOGY:Liposomal formulations were prepared from a mixture of 1,2-Dimyristoyl-sn-Glycero-3-Phosphocholine (DMPC) or 1,2-Dipalmitoyl-sn-Glycero-3-Phosphocholine (DPPC) and Cholesterol (Chol), respectively. Stability of the formulations in different biological milieus and antibacterial activities compared to conventional forms in the presence of the aforementioned inhibitory factors or CF sputum were evaluated. RESULTS:The formulations were stable in all conditions tested with no significant differences compared to the controls. Inhibition of antibiotic formulations by DNA/F-actin and LPS/LTA was concentration dependent. DNA/F-actin (125 to 1000 mg/L) and LPS/LTA (1 to 1000 mg/L) inhibited conventional tobramycin bioactivity, whereas, liposome-entrapped tobramycin was inhibited at higher concentrations--DNA/F-actin (500 to 1000 mg/L) and LPS/LTA (100 to 1000 mg/L). Neither polymyxin B formulation was inactivated by DNA/F-actin, but LPS/LTA (1 to 1000 mg/L) inhibited the drug in conventional form completely and higher concentrations of the inhibitors (100 to 1000 mg/L) was required to inhibit the liposome-entrapped polymyxin B. Co-incubation with inhibitory factors (1000 mg/L) increased conventional (16-fold) and liposomal (4-fold) tobramycin minimum bactericidal concentrations (MBCs), while both polymyxin B formulations were inhibited 64-fold. CONCLUSIONS:Liposome-entrapment reduced antibiotic inhibition up to 100-fold and the CFU of endogenous P. aeruginosa in sputum by 4-fold compared to the conventional antibiotic, suggesting their potential applications in CF lung infections

Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine

[This corrects the article DOI: 10.1186/s13054-016-1208-6.]

Evidence for perinatal and child health care guidelines in crisis settings: can Cochrane help?

<p>Abstract</p> <p>Background</p> <p>It is important that healthcare provided in crisis settings is based on the best available research evidence. We reviewed guidelines for child and perinatal health care in crisis situations to determine whether they were based on research evidence, whether Cochrane systematic reviews were available in the clinical areas addressed by these guidelines and whether summaries of these reviews were provided in Evidence Aid.</p> <p>Methods</p> <p>Broad internet searches were undertaken to identify relevant guidelines. Guidelines were appraised using AGREE and the clinical areas that were relevant to perinatal or child health were extracted. We searched The Cochrane Database of Systematic Reviews to identify potentially relevant reviews. For each review we determined how many trials were included, and how many were conducted in resource-limited settings.</p> <p>Results</p> <p>Six guidelines met selection criteria. None of the included guidelines were clearly based on research evidence. 198 Cochrane reviews were potentially relevant to the guidelines. These reviews predominantly addressed nutrient supplementation, breastfeeding, malaria, maternal hypertension, premature labour and prevention of HIV transmission. Most reviews included studies from developing settings. However for large portions of the guidelines, particularly health services delivery, there were no relevant reviews. Only 18 (9.1%) reviews have summaries in Evidence Aid.</p> <p>Conclusions</p> <p>We did not identify any evidence-based guidelines for perinatal and child health care in disaster settings. We found many Cochrane reviews that could contribute to the evidence-base supporting future guidelines. However there are important issues to be addressed in terms of the relevance of the available reviews and increasing the number of reviews addressing health care delivery.</p

A case-control study of lifestyle risk factors associated with tuberculosis in Liverpool, North-West England

The aim of this study was to identify the subtle influences of exposure and individual lifestyles on the risk of developing tuberculosis. A retrospective case-control study (with matching by sex, age, postcode and ethnicity) of all tuberculosis cases notified over a 7-yr period in Liverpool, UK, was carried out. Multiple logistic regression showed that, before diagnosis, cases were 7.4 times more likely to have had visitors from abroad; 4.0 times more likely to have been born abroad; and 3.8 times more likely to have lived with someone with tuberculosis. Subtle socioeconomic factors were also evident with cases 4.0 times less likely to have additional bathrooms. Lifestyle factors emerged with cases 2.3 times more likely to have smoked for at least 30 yrs, 3.8 times less likely to eat dairy products every week and 2.6 times less likely to have had high blood pressure. At interview, these factors were still evident, but cases, unlike controls, had reduced their smoking and alcohol consumption and were less likely to go out of the home or exercise than before their illness. Within individuals, lifestyle consequences of tuberculosis lead to a "healthier" lifestyle on the one hand (less smoking and alcohol consumption), but a reduced quality of life (social activity) on the other

Interaction between hydrogen sulfide, nitric oxide, and carbon monoxide pathways in the bovine isolated retina

Purpose: Nitric oxide (NO), carbon monoxide (CO) and hydrogen sulfide (H2S) are physiologically relevant gaseous neurotransmitters that are endogenously produced in mammalian tissues. In the present study, we investigated the possibility that NO and CO can regulate the endogenous levels of H2S in bovine isolated neural retina. Methods: Isolated bovine neural retina were homogenized and tissue homogenates were treated with a NO synthase inhibitor, NO donor, heme oxygenase-1 inhibitor, and/donor. H2S concentrations in bovine retinal homogenates were measured using a well-established colorimetric assay. Results: L-NAME (300 nM-500 μM) caused a concentration-dependent decrease in basal endogenous levels of H2S by 86.2%. On the other hand, SNP (10-300 μM) elicited a concentration-related increase in H2S levels from 18.3 nM/mg of protein to 65.7 nM/mg of protein. ZnPP-IX (300 nM-10 μM) caused a concentration-dependent increase in the endogenous production of H2S whereas hemin (300 nM-20 μM) attenuated the basal levels of H2S. Conclusion: We conclude that changes in the biosynthesis and availability of both NO and CO can interfere with the pathway/s involved in the production of H2S in the retina. The demonstrated ability of NO, CO and H2S to interact in the mammalian retina affirms a physiological/pharmacological role for these gaseous mediators in the eye

Country Diagnostic Report, Ethiopa

This report shows how water security threats intersect to create specific risks to Ethiopia’s growth and transformation, and its progress towards its goal to become a middle income country by 2025. It is focused on three specific areas where water insecurity threatens Ethiopia’s efforts to grow and reduce poverty: Water-related risk to growth, A fragile environment and Sustaining Human Development