Recent Advances in the Characterization of Genetic Factors Involved in Human Susceptibility to Infection by Schistosomiasis

Human resistance to infection by schistosomes is associated to a strong Th2 immune. However a persistent Th2 response can cause severe kidney and liver disease in human. In this review, we mainly focused on the control of infection levels caused by schistosomes. Several experimental models allowed us to better understand the immunological mechanisms of the host against schistosome infection. High IgE and eosinophil levels are associated with resistance to infection by schistosomes and this effect is counterbalanced by IgG4. IgE and eosinophils are highly dependent on IL-4, IL-13, and Il-5, which are three main Th2 cytokines. We also examined the genetic factors involved in human susceptibility to infection by schistosomiasis. Infection levels are mainly regulated by a major locus SM1, in 5q31-q33 region, which contains the genes encoding for the IL-4, IL-13, and Il-5 cytokines. An association between an IL13 polymorphism, rs1800925, and infection levels has been shown. This polymorphism synergistically acts with another polymorphism (rs324013) in the STAT6 gene, encoding for the signal transducer of the IL13 pathway. This pathway has also been involved in atopic disorders. As helminthiasis, atopy is the result of aberrant Th2 cytokine response to allergens, with an increased production of IL-4, IL-13, Il-9 and Il-5, with high amounts of allergen-specific and total IgE and eosinophilia. However, the Th2 immune response is protective in helminthiasis but aggravating in atopic disorders. Several studies reported interplay between helminthic infections and allergic reactions. The different results are discussed here

Genetic characterization of a VanG-type vancomycin-resistant Enterococcus faecium clinical isolate

International audienceObjectives: To characterize, phenotypically and genotypically, the first Enterococcus faecium clinical isolate harbouring a vanG operon.Methods: The antibiotic resistance profile of E. faecium 16-346 was determined and its whole genome sequenced using PacBio technology. Attempts to transfer vancomycin resistance by filter mating were performed and the inducibility of expression of the vanG operon was studied by reverse-transcription quantitative PCR (RT-qPCR) in the presence or absence of subinhibitory concentrations of vancomycin.Results: E. faecium 16-346 was resistant to rifampicin (MIC >4 mg/L), erythromycin (MIC >4 mg/L), tetracycline (MIC >16 mg/L) and vancomycin (MIC 8 mg/L), but susceptible to teicoplanin (MIC 0.5 mg/L). The strain harboured the vanG operon in its chromosome, integrated in a 45.5 kb putative mobile genetic element, similar to that of Enterococcus faecalis BM4518. We were unable to transfer vancomycin resistance from E. faecium 16-346 to E. faecium BM4107 and E. faecalis JH2-2. Lastly, transcription of the vanG gene was inducible by vancomycin.Conclusions: This is, to the best of our knowledge, the first report of a VanG-type vancomycin-resistant strain of E. faecium. Despite the alarm pulled because of the therapeutic problems caused by VRE, our work shows that new resistant loci can still be found in E. faecium

EClinicalMedicine

BACKGROUND: As mortality remains high for patients with Ebola virus disease (EVD) despite new treatment options, the ability to level up the provided supportive care and to predict the risk of death is of major importance. This analysis of the EVISTA cohort aims to describe advanced supportive care provided to EVD patients in the Democratic Republic of the Congo (DRC) and to develop a simple risk score for predicting in-hospital death, called PREDS. METHODS: In this prospective cohort (NCT04815175), patients were recruited during the 10(th) EVD outbreak in the DRC across three Ebola Treatment Centers (ETCs). Demographic, clinical, biological, virological and treatment data were collected. We evaluated factors known to affect the risk of in-hospital death and applied univariate and multivariate Cox proportional-hazards analyses to derive the risk score in a training dataset. We validated the score in an internal-validation dataset, applying C-statistics as a measure of discrimination. FINDINGS: Between August 1(st) 2018 and December 31(th) 2019, 711 patients were enrolled in the study. Regarding supportive care, patients received vasopressive drug (n = 111), blood transfusion (n = 101), oxygen therapy (n = 250) and cardio-pulmonary ultrasound (n = 15). Overall, 323 (45%) patients died before day 28. Six independent prognostic factors were identified (ALT, creatinine, modified NEWS2 score, viral load, age and symptom duration). The final score range from 0 to 13 points, with a good concordance (C = 86.24%) and calibration with the Hosmer-Lemeshow test (p = 0.12). INTERPRETATION: The implementation of advanced supportive care is possible for EVD patients in emergency settings. PREDS is a simple, accurate tool that could help in orienting early advanced care for at-risk patients after external validation. FUNDING: This study was funded by ALIMA

Enterococcus spp. : entre pathogènes opportunistes et probiotiques

Enterococci are commensal bacteria of the human and animal gastrointestinal tract, but some species as Enterococcus faecium, are also major opportunistic pathogens often multiply resistant to antibiotics. We studied the impact of non-antibiotic molecules widely used in intensive care units on fitness, virulence and resistance of a clinical isolate of E. faecium belonging to CC17 by a microscopic approach, a peptidoglycan analysis and a trancriptomic analysis. This work allowed us to demonstratethe antimicrobial effect of caspofungin, molecule known for its antifungal activity. We also characterized two novel resistance mechanisms found in E. faecium: i) resistance to lincosamides, streptogramines A and pleuromutilins (LSAP phenotype) linked to a point mutation in a gene encoding for a type-II ABC protein. ii) decreased susceptibility to tigecycline due to the occurrence of mutations within the rpsJ gene encoding the S10 ribosomal protein that plays a role in 30S ribosomal subunit formation. Finally, we participated to a study concerning Enterococcus hirae, species that induces the production of sub-populations of T lymphocytes that increase the in vivo efficacy of cyclophosphamide (CTX) in the treatment of murine tumors. A characterization of the virulence factors, antibiotic resistance profiles and colonization capacities of a collection of E. hirae isolates was carried out. A transcriptomic study in the presence of CTX and a comparative genomic study were also done, in order to characterize this species in view of its use as an oncobiotic.Les entérocoques, sont des bactéries commensales du tube digestif de l’homme et des animaux, mais certaines espèces, comme Enterococcus faecium, sont aussi des pathogènes opportunistes majeurs souvent multi-résistants aux antibiotiques. Nous avons étudié l’impact de molécules non antibiotiques utilisées dans les unités de soins intensifs, sur la virulence et la résistance d’une souche clinique de E. faecium par une approche microscopique, une analyse du peptidoglycane et une analyse trancriptomique. Ce travail nous a permis de décrire l’effet antibactérien de la caspofungine, molécule antifongique. Nous avons également étudié deux nouveaux mécanismes de résistance chez E. faecium i) la résistance aux lincosamides, streptogramines A et pleuromutilines (phénotype LSAP) par la mutation ponctuelle d’un gène codant pour une protéine ABC de type II. ii) la diminution de sensibilité à la tigécycline due à l’apparition de mutations au sein du gène rpsJ codant pour la protéine ribosomale S10 jouant un rôle dans la formation de la sous-unité 30S du ribosome. Enfin, nous avons participé à une étude sur Enterococcus hirae, espèce qui induirait la production de sous-populations de lymphocytes T permettant d’augmenter l’efficacité in vivo du cyclophosphamide (CTX) dans le traitement de tumeurs chez la souris. Une caractérisation des facteurs de virulence, de la résistance aux antibiotiques et du pouvoir de colonisation d’une collection de souches d’E. hirae a été menée, de même qu’une étude transcriptomique en présence de CTX et une étude de génomique comparative, afin de caractériser cette espèce dans l’optique de son utilisation comme oncobiotique

Enterococcus spp. : from opportunistic pathogens to probiotics

Les entérocoques, sont des bactéries commensales du tube digestif de l’homme et des animaux, mais certaines espèces, comme Enterococcus faecium, sont aussi des pathogènes opportunistes majeurs souvent multi-résistants aux antibiotiques. Nous avons étudié l’impact de molécules non antibiotiques utilisées dans les unités de soins intensifs, sur la virulence et la résistance d’une souche clinique de E. faecium par une approche microscopique, une analyse du peptidoglycane et une analyse trancriptomique. Ce travail nous a permis de décrire l’effet antibactérien de la caspofungine, molécule antifongique. Nous avons également étudié deux nouveaux mécanismes de résistance chez E. faecium i) la résistance aux lincosamides, streptogramines A et pleuromutilines (phénotype LSAP) par la mutation ponctuelle d’un gène codant pour une protéine ABC de type II. ii) la diminution de sensibilité à la tigécycline due à l’apparition de mutations au sein du gène rpsJ codant pour la protéine ribosomale S10 jouant un rôle dans la formation de la sous-unité 30S du ribosome. Enfin, nous avons participé à une étude sur Enterococcus hirae, espèce qui induirait la production de sous-populations de lymphocytes T permettant d’augmenter l’efficacité in vivo du cyclophosphamide (CTX) dans le traitement de tumeurs chez la souris. Une caractérisation des facteurs de virulence, de la résistance aux antibiotiques et du pouvoir de colonisation d’une collection de souches d’E. hirae a été menée, de même qu’une étude transcriptomique en présence de CTX et une étude de génomique comparative, afin de caractériser cette espèce dans l’optique de son utilisation comme oncobiotique.Enterococci are commensal bacteria of the human and animal gastrointestinal tract, but some species as Enterococcus faecium, are also major opportunistic pathogens often multiply resistant to antibiotics. We studied the impact of non-antibiotic molecules widely used in intensive care units on fitness, virulence and resistance of a clinical isolate of E. faecium belonging to CC17 by a microscopic approach, a peptidoglycan analysis and a trancriptomic analysis. This work allowed us to demonstratethe antimicrobial effect of caspofungin, molecule known for its antifungal activity. We also characterized two novel resistance mechanisms found in E. faecium: i) resistance to lincosamides, streptogramines A and pleuromutilins (LSAP phenotype) linked to a point mutation in a gene encoding for a type-II ABC protein. ii) decreased susceptibility to tigecycline due to the occurrence of mutations within the rpsJ gene encoding the S10 ribosomal protein that plays a role in 30S ribosomal subunit formation. Finally, we participated to a study concerning Enterococcus hirae, species that induces the production of sub-populations of T lymphocytes that increase the in vivo efficacy of cyclophosphamide (CTX) in the treatment of murine tumors. A characterization of the virulence factors, antibiotic resistance profiles and colonization capacities of a collection of E. hirae isolates was carried out. A transcriptomic study in the presence of CTX and a comparative genomic study were also done, in order to characterize this species in view of its use as an oncobiotic

Kurtze und Gründtliche Underweisung/ Wie die weisse Maulbeer-Bäum/ in disen Landen auff underschidliche Weiß/ zu Erzüglung der Seyden-Würmen, dem allgemainen Wesen zum besten/ sollen gepflantzt werden : Sambt einem außführlichen Bericht/ Wie die Seyden-Würm ernehret/ auffgebracht/ underhalten: Die Seyden abgewunden/ auffgehaspelt/ zuegericht und genutzet werden solle. Allen und jeden der Seyden-Manufacturen/ und deß gemeinen Nutzens Liebhabern zum Guetem. Auff gnädige Verordnung/ Auß dem Frantzösischen in das Hochteutsche übersetzt/ und in offentlichen Truck gegeben

Autor (Christoph Isnard) nach VD17 (Verf. ermittelt in: BL (German books)). - Herausgeber (Georg Kapffer) in der Widmung genanntProvenienzvermerk auf vorderem Spiegel "Universitäts-Bibliothek Basel Geschenk v.Hr. Sarasin-Warnery 1904" sowie Besitzerstempel Vorsatzblatt "Reinhold Sarasin-Warnery"Aufkleber auf hinterem Spiegel: "Max Harrwitz Buchhandlung & Antiquariat Berlin W. Potsdamerstr. 41 A

Neue Seiden-Manufactur, Das ist: Ausführliche Erzehlung/ Wie Maulbeer-Bäume und Seiden-Würme gepfleget/ gewartet/ fortgepflantzet/ und die darzu bereitete Seide recht zugerichtet und genutzet werden könne

Aus langwieriger und eigener Erfahrung Jn Vier Theilen Wohlmeinend fürgestellet von dem Kunstliebenden4 KupfersticheVerfasser nach VD17: Christoph IsnardProvenienzvermerk auf vorderem Spiegel: "Universitäts-Bibliothek Basel. Geschenk v. Hr. Sarasin-Warnery 1904" und Besitzerstempel auf Vorsatzblatt 21.01.2016/A100/OA

Experimental Study of a Turbulent Liquid Flame.

International audienc

Association of rs7719175, located in the IL13 gene promoter, with Schistosoma haematobium infection levels and identification of a susceptibility haplotype

International audienceno abstrac