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Archive - Feb 20, 2015

Powerful Neutralizing Dengue Antibody Found

A new Duke-National University of Singapore (Duke-NUS)-led study has identified a super-potent human monoclonal antibody that requires just a minute amount to neutralize the dengue virus. This significant advance, published online on February 20, 2015, in an open-access article in Nature Communications, shows how a newly identified antibody, 5J7, is highly effective in killing dengue virus; only 10-9 g of antibody is needed to stop the infection of dengue serotype 3 virus (DENV-3). The authors report that DENV-specific antibody 5J7 is exceptionally potent, neutralizing 50% of virus at nanogram-range antibody concentration. This new finding gives hope for the development of effective dengue treatments. The authors further report that cryo-electron microscopy analysis of the Fab 5J7–DENV complex shows that a single Fab molecule binds across three envelope proteins and engages three functionally important domains, each from a different envelope protein. These domains are critical for receptor binding and fusion to the endosomal membrane. The ability to bind to multiple domains allows the 5J7 antibody to fully coat the dengue virus surface with only 60 copies of Fab, that is, half the amount compared with other potent antibodies. The authors say that their study of 5J7 reveals a highly efficient and unusual mechanism of molecular recognition by an antibody. Their article is titled “A Highly Potent Human Antibody Neutralizes Dengue Virus Serotype 3 by Binding across Three Surface Proteins.” Over the last 50 years, the incidence of dengue virus infection has increased by 30 times worldwide. The virus causes fever, rashes, and joint pain and, in severe cases, bleeding and shock. It is estimated to be endemic in 100 countries and is a huge burden on healthcare systems.

Bacteria Specifically Adapt Their Metabolism to Host Genotype; Results Imply Form of Bacterial “Memory”

Bacteria are masters at adapting to their environment. This adaptability contributes to the bacteria’s survival inside the host. Researchers at the Vetmeduni Vienna in Austria have now demonstrated that the bacterial pathogen Listeria monocytogenes adapts its metabolism specifically to the host genotype. The bacterial metabolic fingerprint correlated with the susceptibility of the infected mouse strain. The researchers published their results online in the open-access journal PLOS ONE on December 26, 2014. The title of the article is “Deciphering Host Genotype-Specific Impacts on the Metabolic Fingerprint of Listeria monocytogenes by FTIR Spectroscopy.” Understanding such adaptation mechanisms is crucial for the development of effective therapeutics. Dr, Monika Ehling-Schulz’s group from the Institute of Microbiology, together with Dr. Mathias Müller’s group at the Institute of Animal Breeding and Genetics studied the influence of host organisms on bacterial metabolism. The researchers infected three different lineages of mice with the bacteria Listeria monocytogenes. The mouse strains showed significant differences in their response to the infection and in the severity of their clinical symptoms. The researchers isolated the bacteria days after infection and analyzed them for changes in their metabolism. The scientists used a specific infrared spectroscopy method (FTIR) (see below) to monitor metabolic changes. The chemometric analysis of the bacterial metabolic fingerprints revealed host genotype specific imprints and adaptations of the bacterial pathogen. “Our findings may have implications on how to treat infectious diseases in general. Every patient is different and so are their bacteria,” first author Dr. Tom Grunert states.

Powerful New Scanning Transmission Electron Microscope (STEM) Can See and Pinpoint Single Atoms

A new super-powerful electron microscope that can pinpoint the position of single atoms, and will help scientists push boundaries even further, in fields such as advanced materials, healthcare, and power generation, was unveiled February 19, 2015 by the Engineering and Physical Sciences Research Council (EPSRC). The £3.7 million Nion Hermes Scanning Transmission Electron Microscope, one of only three in the world, will be sited at the EPSRC SuperSTEM facility at the Daresbury laboratory complex near Warrington, UK, which is part of the Science and Technology Facilities Council (STFC). The new microscope not only allows imaging of unprecedented resolution of objects a million times smaller than a human hair, but also analysis of materials. This means that researchers will not only be able to clearly identify the atoms, but observe the strength of the bonds between them. This will improve understanding of their electronic properties when in bulk and how they may perform when used. Minister for Universities, Science, and Cities, Greg Clark, said: “The UK is a world leader in the development and application of STEM (Scanning Transmission Electron Microscope) techniques, and this new super-powerful microscope will ensure we remain world-class. From developing new materials for space travel to creating a better, cheaper treatment for anaemia, this new super-powerful microscope lets UK scientists examine how materials behave at a level a million times smaller than a human hair. This exciting research will help lead to breakthroughs that will benefit not only our health but the environment too.” Professor Philip Nelson, EPSRC’s Chief Executive said: “This EPSRC investment in state-of-the-art equipment is an investment in UK science and engineering.