Weltweiter SARS-Alarm : eine neue Seuche auf dem Vormarsch?

Mitte März 2003 löste die WHO einen weltweiten Alarm aus, nachdem sich eine neuartige, schwere und unter bestimmten Umständen hochansteckende Atemwegserkrankung scheinbar unaufhaltsam über weite Teile der Welt auszubreiten schien. Am 15. März desselben Jahres landeten die ersten Patienten mit Verdacht auf Schweres Akutes Respiratorisches Syndrom (SARS) in Frankfurt und wurden auf die Isolierstation des Universitätsklinikums aufgenommen. Auslöser war ein zuvor nicht bekanntes Coronavirus, das heute als SARS-CoV bezeichnet wird. Derzeit laufen Untersuchungen zur Biologie und Epidemiologie des neuen Erregers, zu antiviralen Hemmstoffen sowie zu Desinfektions- und Inaktivierungsmöglichkeiten und neuen Therapieoptionen. Daneben wird analysiert, wie sich das öffentliche Gesundheitswesen auf eine mögliche Wiederkehr vorbereiten muss. SARS ist ein Beispiel dafür, wie schnell sich eine Infektionskrankheit in der modernen Welt international ausbreiten kann und wie wichtig in einem solchen Falle eine gut koordinierte internationale Kooperation ist. Frankfurter Forscher berichten

A universal strategy for high-yield production of soluble and functional clostridial collagenases in E. coli

Clostridial collagenases are foe and friend: on the one hand, these enzymes enable host infiltration and colonization by pathogenic clostridia, and on the other hand, they are valuable biotechnological tools due to their capacity to degrade various types of collagen and gelatine. However, the demand for high-grade preparations exceeds supply due to their pathogenic origin and the intricate purification of homogeneous isoforms. We present the establishment of an Escherichia coli expression system for a variety of constructs of collagenase G (ColG) and H (ColH) from Clostridium histolyticum and collagenase T (ColT) from Clostridium tetani, mimicking the isoforms in vivo. Based on a setup of five different expression strains and two expression vectors, 12 different constructs were expressed, and a flexible purification platform was established, consisting of various orthogonal chromatography steps adaptable to the individual needs of the respective variant. This fast, cost-effective, and easy-to-establish platform enabled us to obtain at least 10 mg of highly pure mono-isoformic protein per liter of culture, ideally suited for numerous sophisticated downstream applications. This production and purification platform paves the way for systematic screenings of recombinant collagenases to enlighten the biochemical function and to identify key residues and motifs in collagenolysis

The heme sensing response regulator HssR in Staphylococcus aureus but not the homologous RR23 in Listeria monocytogenes modulates susceptibility to the antimicrobial peptide plectasin

<p>Abstract</p> <p>Background</p> <p>Host defence peptides (HDPs), also known as antimicrobial peptides (AMPs), have emerged as potential new therapeutics and their antimicrobial spectrum covers a wide range of target organisms. However, the mode of action and the genetics behind the bacterial response to HDPs is incompletely understood and such knowledge is required to evaluate their potential as antimicrobial therapeutics. Plectasin is a recently discovered HDP active against Gram-positive bacteria with the human pathogen, <it>Staphylococcus aureus </it>(<it>S. aureus</it>) being highly susceptible and the food borne pathogen, <it>Listeria monocytogenes </it>(<it>L. monocytogenes</it>) being less sensitive. In the present study we aimed to use transposon mutagenesis to determine the genetic basis for <it>S. aureus </it>and <it>L. monocytogenes </it>susceptibility to plectasin.</p> <p>Results</p> <p>In order to identify genes that provide susceptibility to plectasin we constructed bacterial transposon mutant libraries of <it>S. aureus </it>NCTC8325-4 and <it>L. monocytogenes </it>4446 and screened for increased resistance to the peptide. No resistant mutants arose when <it>L. monocytogenes </it>was screened on plates containing 5 and 10 fold Minimal Inhibitory Concentration (MIC) of plectasin. However, in <it>S. aureus</it>, four mutants with insertion in the heme response regulator (<it>hssR</it>) were 2-4 fold more resistant to plectasin as compared to the wild type. The <it>hssR </it>mutation also enhanced resistance to the plectasin-like defensin eurocin, but not to other classes of HDPs or to other stressors tested. Addition of plectasin did not influence the expression of <it>hssR </it>or <it>hrtA</it>, a gene regulated by HssR. The genome of <it>L. monocytogenes </it>LO28 encodes a putative HssR homologue, RR23 (in <it>L. monocytogenes </it>EGD-e lmo2583) with 48% identity to the <it>S. aureus </it>HssR, but a mutation in the <it>rr23 </it>gene did not change the susceptibility of <it>L. monocytogenes </it>to plectasin.</p> <p>Conclusions</p> <p><it>S. aureus </it>HssR, but not the homologue RR23 from <it>L. monocytogenes</it>, provides susceptibility to the defensins plectasin and eurocin. Our data suggest that a functional difference between response regulators HssR and RR23 is responsible for the difference in plectasin susceptibility observed between <it>S. aureus </it>and <it>L. monocytogenes</it>.</p

Functions and Requirements of the CMS Centre at CERN

This report of the CMS Centre Requirements and Technical Assessment Group describes the functions of the CMS Centre on the CERN Meyrin site in terms of data quality monitoring, calibrations and rapid analysis and operations of the offline computing systems. It then defines the corresponding requirements for building space, computing consoles and other equipment, technical services and refurbishments, and communications systems

Isolation facilities for highly infectious diseases in Europe - A cross-sectional analysis in 16 countries

BACKGROUND: Highly Infectious Diseases (HIDs) are (i) easily transmissible form person to person; (ii) cause a life-threatening illness with no or few treatment options; and (iii) pose a threat for both personnel and the public. Hence, even suspected HID cases should be managed in specialised facilities minimizing infection risks but allowing state-of-the-art critical care. Consensus statements on the operational management of isolation facilities have been published recently. The study presented was set up to compare the operational management, resources, and technical equipment among European isolation facilities. Due to differences in geography, population density, and national response plans it was hypothesized that adherence to recommendations will vary. METHODS AND FINDINGS: Until mid of 2010 the European Network for Highly Infectious Diseases conducted a cross-sectional analysis of isolation facilities in Europe, recruiting 48 isolation facilities in 16 countries. Three checklists were disseminated, assessing 44 items and 148 specific questions. The median feedback rate for specific questions was 97.9% (n = 47/48) (range: n = 7/48 (14.6%) to n = 48/48 (100%). Although all facilities enrolled were nominated specialised facilities' serving countries or regions, their design, equipment and personnel management varied. Eighteen facilities fulfilled the definition of a High Level Isolation Unit'. In contrast, 24 facilities could not operate independently from their co-located hospital, and five could not ensure access to equipment essential for infection control. Data presented are not representative for the EU in general, as only 16/27 (59.3%) of all Member States agreed to participate. Another limitation of this study is the time elapsed between data collection and publication; e.g. in Germany one additional facility opened in the meantime. CONCLUSION: There are disparities both within and between European countries regarding the design and equipment of isolation facilities. With regard to the International Health Regulations, terminology, capacities and equipment should be standardised

Developmental programming of cardiovascular dysfunction by prenatal hypoxia and oxidative stress.

Fetal hypoxia is a common complication of pregnancy. It has been shown to programme cardiac and endothelial dysfunction in the offspring in adult life. However, the mechanisms via which this occurs remain elusive, precluding the identification of potential therapy. Using an integrative approach at the isolated organ, cellular and molecular levels, we tested the hypothesis that oxidative stress in the fetal heart and vasculature underlies the molecular basis via which prenatal hypoxia programmes cardiovascular dysfunction in later life. In a longitudinal study, the effects of maternal treatment of hypoxic (13% O(2)) pregnancy with an antioxidant on the cardiovascular system of the offspring at the end of gestation and at adulthood were studied. On day 6 of pregnancy, rats (n = 20 per group) were exposed to normoxia or hypoxia ± vitamin C. At gestational day 20, tissues were collected from 1 male fetus per litter per group (n = 10). The remaining 10 litters per group were allowed to deliver. At 4 months, tissues from 1 male adult offspring per litter per group were either perfusion fixed, frozen, or dissected for isolated organ preparations. In the fetus, hypoxic pregnancy promoted aortic thickening with enhanced nitrotyrosine staining and an increase in cardiac HSP70 expression. By adulthood, offspring of hypoxic pregnancy had markedly impaired NO-dependent relaxation in femoral resistance arteries, and increased myocardial contractility with sympathetic dominance. Maternal vitamin C prevented these effects in fetal and adult offspring of hypoxic pregnancy. The data offer insight to mechanism and thereby possible targets for intervention against developmental origins of cardiac and peripheral vascular dysfunction in offspring of risky pregnancy