Differences in Acinetobacter baumannii Strains and Host Innate Immune Response Determine Morbidity and Mortality in Experimental Pneumonia

Despite many reports documenting its epidemicity, little is known on the interaction of Acinetobacter baumannii with its host. To deepen our insight into this relationship, we studied persistence of and host response to different A. baumannii strains including representatives of the European (EU) clones I–III in a mouse pneumonia model. Neutropenic mice were inoculated intratracheally with five A. baumannii strains and an A. junii strain and at several days morbidity, mortality, bacterial counts, airway inflammation, and chemo- and cytokine production in lungs and blood were determined. A. baumannii RUH875 and RUH134 (EU clone I and II, respectively) and sporadic strain LUH8326 resulted in high morbidity/mortality, whereas A. baumannii LUH5875 (EU clone III, which is less widespread than clone I and II) caused less symptoms. A. baumannii type strain RUH3023T and A. junii LUH5851 did not cause disease. All strains, except A. baumannii RUH3023T and A. junii LUH5851, survived and multiplied in the lungs for several days. Morbidity and mortality were associated with the severity of lung pathology and a specific immune response characterized by low levels of anti-inflammatory (IL-10) and specific pro-inflammatory (IL-12p40 and IL-23) cytokines at the first day of infection. Altogether, a striking difference in behaviour among the A. baumannii strains was observed with the clone I and II strains being most virulent, whereas the A. baumannii type strain, which is frequently used in virulence studies appeared harmless

Diversity in Acinetobacter baumannii isolates from paediatric cancer patients in Egypt

Acinetobacter baumannii is an important nosocomial pathogen, commonly causing infections in immunocompromised patients. It is increasingly reported as a multidrug-resistant organism, which is alarming because of its capability to resist all available classes of antibiotics including carbapenems. The aim of this study was to examine the genetic and epidemiological diversity of A. baumannii isolates from paediatric cancer patients in Egypt, by sequencing the intrinsic blaOXA -51-like gene, genotyping by pulsed-field gel electrophoresis and multi-locus sequence typing in addition to identifying the carbapenem-resistance mechanism. Results showed a large diversity within the isolates, with eight different blaOXA -51-like genes, seven novel sequence types and only 28% similarity by pulsed-field gel electrophoresis. All three acquired class-D carbapenemases (OXA-23, OXA-40 and OXA-58) were also identified among these strains correlating with resistance to carbapenems. In addition, we report the first identification of ISAba2 upstream of blaOXA -51-like contributing to high-level carbapenem resistance. This indicates the presence of several clones of A. baumannii in the hospitals and illustrates the large genetic and epidemiological diversity found in Egyptian strains

Do Biofilm Formation and Interactions with Human Cells Explain the Clinical Success of Acinetobacter baumannii?

BACKGROUND: The dramatic increase in antibiotic resistance and the recent manifestation in war trauma patients underscore the threat of Acinetobacter baumannii as a nosocomial pathogen. Despite numerous reports documenting its epidemicity, little is known about the pathogenicity of A. baumannii. The aim of this study was to obtain insight into the factors that might explain the clinical success of A. baumannii. METHODOLOGY/PRINCIPAL FINDINGS: We compared biofilm formation, adherence to and inflammatory cytokine induction by human cells for a large panel of well-described strains of A. baumannii and compared these features to that of other, clinically less relevant Acinetobacter species. Results revealed that biofilm formation and adherence to airway epithelial cells varied widely within the various species, but did not differ among the species. However, airway epithelial cells and cultured human macrophages produced significantly less inflammatory cytokines upon exposure to A. baumannii strains than to strains of A. junii, a species infrequently causing infection. CONCLUSION/SIGNIFICANCE: The induction of a weak inflammatory response may provide a clue to the persistence of A. baumannii in patients

Contribution of Red Blood Cells and Platelets to Blood Clot Computed Tomography Imaging and Compressive Mechanical Characteristics

Thrombus computed tomography (CT) imaging characteristics may correspond with thrombus mechanical properties and thus predict thrombectomy success. The impact of red blood cell (RBC) content on these properties (imaging and mechanics) has been widely studied. However, the additional effect of platelets has not been considered. The objective of the current study was to examine the individual and combined effects of blood clot RBC and platelet content on resultant CT imaging and mechanical characteristics. Human blood clot analogues were prepared from a combination of preselected RBC volumes and platelet concentrations to decouple their contributions. The resulting clot RBC content (%) and platelet content (%) were determined using Martius Scarlet Blue and CD42b staining, respectively. Non-contrast and contrast-enhanced CT (NCCT and CECT) scans were performed to measure the clot densities. CECT density increase was taken as a proxy for clinical perviousness. Unconfined compressive mechanics were analysed by performing 10 cycles of 80% strain. RBC content is the major determinant of clot NCCT density. However, additional consideration of the platelet content improves the association. CECT density increase is influenced by clot platelet and not RBC content. Platelet content is the dominant component driving clot stiffness, especially at high strains. Both RBC and platelet content contribute to the clot's viscoelastic and plastic compressive properties. The current in vitro results suggest that CT density is reflective of RBC content and subsequent clot viscoelasticity and plasticity, and that perviousness reflects the clot's platelet content and subsequent stiffness. However, these indications should be confirmed in a clinical stroke cohort

Current molecular methods in epidemiological typing of Acinetobacter baumannii

International audienc

The Population Structure of Acinetobacter baumannii: Expanding Multiresistant Clones from an Ancestral Susceptible Genetic Pool

Outbreaks of hospital infections caused by multidrug resistant Acinetobacter baumannii strains are of increasing concern worldwide. Although it has been reported that particular outbreak strains are geographically widespread, little is known about the diversity and phylogenetic relatedness of A. baumannii clonal groups. Sequencing of internal portions of seven housekeeping genes (total 2,976 nt) was performed in 154 A. baumannii strains covering the breadth of known diversity and including representatives of previously recognized international clones, and in 19 representatives of other Acinetobacter species. Restricted amounts of diversity and a star-like phylogeny reveal that A. baumannii is a genetically compact species that suffered a severe bottleneck in the recent past, possibly linked to a restricted ecological niche. A. baumannii is neatly demarcated from its closest relative (genomic species 13TU) and other Acinetobacter species. Multilocus sequence typing analysis demonstrated that the previously recognized international clones I to III correspond to three clonal complexes, each made of a central, predominant genotype and few single locus variants, a hallmark of recent clonal expansion. Whereas antimicrobial resistance was almost universal among isolates of these and a novel international clone (ST15), isolates of the other genotypes were mostly susceptible. This dichotomy indicates that antimicrobial resistance is a major selective advantage that drives the ongoing rapid clonal expansion of these highly problematic agents of nosocomial infections

Studien uber heterogenetische Antigene der Hornmasse des Pferdes

Von den drei Hornmassenarten (Huf, Kastanie und Sporn), welche an der Oberhaut des Pferdes vorhanden sind, prufte ich das Vorkommen heterogenetischer Antigene und untersuchte zugleich das durch diese Antigene hervorgerufene Verwandtschaftsverhaltnis der Hornmassen zueinander. Die Kaninchen wurden entweder mit einem Extrakte immunisiert, das aus dem zu untersuchenden Material mit physiologischer Kochsalzlosung als Medium hergestellt war (Emulsion), oder mittels eines unter Erwarmung bereiteten alkoholischen Auszugs (Lipoide). Auf diese Weise wurde versucht, die Antigene in vivo festzustellen. Dann wurden die Antigene noch in vitro einer Untersuchung unterzogen. Die Ergebnisse dieser Studien sind kurz folgende: 1. Der Hornstoff des Hufes enthalt heterogenetisches Antigen. Besonderes Interesse beansprucht jedoch dabei die Beobachtung, dass selbst bei ein und demselben Huf je nach der Stelle der Antigen-Titer des Hornstoffes in weiten Grenzen schwankt. 2. Der Kastanienhornstoff hat heterogenetisches Antigen. 3. Auch beim Spornhornstoff findet sich heterogenetisches Antigen. 4. Wenn man die aus diesen drei Hornmassen gewonnenen heterogenetischen Antigene mit dem bekannten Antigen, welches den Organen des Meerschweinchens und den Erythrozyten des Schafes gemeinsam ist, vergleicht, so erkennt man, dass alle diese Antigene quantitativ wesentlich verschieden sind. Die ersten drei stehen namlich im allgemeinen dem letzteren nach, wahrend sie aber qualitativ miteinander in Einklang stehen. Uber die Verteilung des heterogenetischen Antigens in den Hornmassen soll folgende Tabelle nach dem Immunisierungsindex Aufschluss geben. 5. Das heterogenetische Antigen ist im Lipoid enthalten und stellt das sogenannte Hapten dar. Dieses Lipoid entfaltet im lebenden Korper als Schlepper erst durch Zusatz von Eiweissbestandteilen Vollantigenitat. 6. Alle Reaktionen mit heterogenetischen Antikorpern ergaben kein so zuverlassiges Resultat, aus dem man auf einen Verwandtschaftsgrad zwischen den Hornmassen hatte schliessen konnen. Kastan

Noordwijker Middengebied, van visie naar plan

Het Middengebied bevindt zich tussen de kernen van de gemeente Noordwijk, Noordwijk aan Zee en Noordwijk Binnen. De afgelopen decennia is dit gebied steeds verder volgebouwd. De druk op de resterende 'open'ruimte is groot. De huidige economische pijlers in de regio beginnen hun vitaliteit te verliezen en het tekort aan beschikbare ruimte om te bouwen maakt dat de druk op de open ruimte verder toeneemt. De gemeente Noordwijk wil het Middengebied duurzaam open houden. Zij wil door middel van een kwaliteitsimpuls het landschap robuust maken