Ökologie, Virulenz und Genomanalyse von Legionella pneumophila Isolaten aus der West Bank, Palästina

Legionella pneumophila is an environmental bacterium and a human pathogen causing life-threating outbreaks of an atypical pneumonia called Legionnaires’ disease. This study aimed to understand the diversity of L. pneumophila isolates, their clonal populations and the environmental driver of their abundance and prevalence in the West Bank. For this, a multi-annual seasonal sampling of nine drinking water sites in the West Bank were performed with a detailed recording of physico-chemical parameters. A total of 180 L. pneumophila isolates were obtained and analysed by high resolution genotyping (Multi-Locus Variable Number of Tandem Repeats (MLVA-8(12)). Also, physiological and virulence traits were studied. Genotyping and the studied traits led to the selection of representative strains submitted to high through-put genome sequencing (Illumina HiSeq and Pacific Biosciences platforms). Analysis of genotype prevalence in correspondence to environmental factors was used to elucidate genotype consortia and their environmental niches. The 180 isolates represented twenty-six individual MLVA-8(12) genotypes (Gt). The most frequently genotype was Gt4(17) (41.1%). All MLVA genotypes were clustered into four MLVA clonal complexes. Analysis of the prevalence of genotype indicated genotype consortia that seemed to be triggered by a set of environmental drivers. The concentration of several ions (Mg, Ca, Cl, SO4 and TDS) and turbidity seemed to determine niches for three different sets of genotypes and may explain their regional variability. Also, the abundance of L. pneumophila was influenced by these environmental drivers with Mg having a negative effect. The virulence of a representative subset of sixty environmental strains was assessed by five different in-vitro assays. Virulence traits were shown to be genotype dependent. A carefully selected subset of thirty-eight L. pneumophila isolates were genome sequenced and compared to already published reference genomes. Genome sequences were aligned with the sequence of the respective reference genome and analysed with respect to core-single nucleotide polymorphisms (core-SNPs), genomic islands and genes related to virulence traits. Overall, this study provided important insights into detailed population structure, the ecology and pathogenicity of this pathogen in the West Bank.Legionella pneumophila ist ein Umweltbakterium in Süsswassersystemen und humanpathogen; es verursacht lebensbedrohliche Ausbrüche der Legionärskrankheit, einer atypischen Pneumonie. Das Ziel der Doktorarbeit ist es, in der West Bank die Diversität von L. pneumophila-Isolaten, ihre clonale Populationsstruktur und die wesentlichen Umweltfaktoren, die Abundanz und Prävalenz steuern, zu verstehen. Hierzu wurde ein mehrjähriges saisonales Probenahmeprogramm für 9 Trinkwasserprobe-nahmestellen repräsentatv für die West Bank durchgeführt, bei dem physico-chemische und mikrobiologische Parameter mitaufgezeichnet wurden. 180 Isolate wurden hierbei gewonnen, hochauflösend genotypisiert (Multi-Locus Variable Number of Tandem Repeats (MLVA-8(12)), und hinsichtlich relevanter physiologischer Eigenschaften und Virulenzfaktoren analysiert. Die umfassende Charakterisierung der Isolate bildete die Grundlage zur Auswahl repräsentativer Stämme für die Genomsequenzierung mittels Illumina HiSeq und der Pac-Biosciences Platform. Die statistische Analyse von regionaler Genotypprävalenz und Umweltfaktoren wurde dazu genutzt um Genotypkonsortien und ihre Umweltnischen zu charakterisieren. Die 180 Isolate aus der Westbank zeigten eine hohe Genotypdiversität von 26 MLVA-8(12)-Genotypen, zugehörig zu vier MLVA clonalen Komplexen. Analysen der Prävalenz von Genotypen im Hinblick auf Umweltfaktoren zeigte, daß Konsortien von Genotypen durch Umweltfaktoren getriggert wurden. Unterschiedliche Konzentrationen von Ionen im Trinkwasser (Mg, Ca, Cl, SO4, TDS) and Trübung schienen Nischen für drei unterschiedliche Konsortien von Genotypen zu bestimmen, und könnten die räumliche Variabilität der Genotypen in der West Bank erklären und die Abundanz von L. pneumophila zu beeinflussen. Dabei schien Mg eine relevante Rolle zu spielen. Die Virulenz einer repräsentativen Untergruppe von 60 Isolaten wurde mit 5 in-vitro Ansätzen getestet. Die Virulenzstärke variierte in Abhängigkeit vom Genotyp mit relativ hoher Virulenz der häufigen Genotypen Gt4(17) und Gt6(18). Eine repräsentative Auswahl von 38 L. pneumophila Isolaten wurden genomsequenziert und mit Referenzgenomen und generierten eigenen Referenzgenomen verglichen, und hinsichtlich core-SNPs, genomischen Inseln und Virulenz-assoziierten Genen analysiert. Insgesamt gesehen, liefert die vorliegende Studie wichtige Einblicke zum Verständnis von Populationsstruktur, Ökologie und Pathogenität dieses pathogenen Bakteriums in der West Bank

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome

Phytoremediation of soils contaminated with heavy metals: techniques and strategies

Environmental pollution by heavy metals and metalloids has become a severe problem worldwide, as soils became increasingly contaminated, posing a threat to ecosystems and ultimately to human health. The decision to remediate a soil depends on the present and future value of the soil, the cost of remediation, the risk posed by the soil, and the perception of that risk by the population and decision-makers. Traditional technologies to remediate soils usually rely on excavation of the contaminated soil, often disposed of as a hazardous waste with or without a previous treatment. The use of plants to remove or immobilize toxic elements has arisen as a very promising alternative to conventional technologies. The use of plants to remediate soils derived from the observation of wild species found in specific environments, evolved to the use of fast growing crops, and later on led to the development of genetically-modified plants. Phytotechnologies include a wide range of technologies that can be applied to remediate soils through stabilization, volatilization, accumulation and sequestration of toxic metals. In this chapter we describe the impacts of heavy metals in plants and the most important phytotechnologies available to remediate soil and substrates