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Archive for May 12th, 2006

New Treatment For Food Poisoning

Posted by tumicrobiology on May 12, 2006

A team of researchers working at the University of Bristol has found a potential new treatment for listeriosis, a deadly form of food poisoning. Their work is reported in Nature Medicine.

The group, led by Professor Jose Vazquez-Boland, has shown that one particular antibiotic — fosfomycin — can treat Listeria in the body, despite it being ineffective in laboratory conditions.

Because it was not effective in the laboratory, this drug has never been considered for the treatment of listeriosis, in spite of it reaching the infection sites more effectively than other antibiotics.

Professor Vazquez-Boland said: “Our results illustrate that antibiotic resistance in the laboratory does not always mean that the drug will not work in the infected patient. This work brings some optimism to the highly worrying problem of the increasing resistance to antibiotics.”

The Listeria bacteria causes the food-borne disease, listeriosis. It often triggers a brain infection and kills up to 30% of those affected.

To test whether antibiotics are effective, bacteria are taken from patients and tested in the laboratory. These tests measure whether antibiotics can halt the growth of Listeria in laboratory conditions. Such tests are usually a measure of how effective the drug will be in the body.

When tested this way, Listeria had been shown to be resistant to the antibiotic, fosfomycin. As a consequence, this drug has never been considered for the treatment of listeriosis.

Dr Mariela Scortti, lead author on the paper, added: “Our findings warn about the need to revise laboratory methods currently in use to determine the susceptibility or resistance of bacteria to such drugs, so that the tests reflect better what actually happens in the body.”
Source: University of Bristol

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How Bad Is Malaria Anemia? It May Depend On Your Genes

Posted by tumicrobiology on May 12, 2006

Cell and animal studies conducted jointly by scientists at Johns Hopkins, Yale and other institutions have uncovered at least one important contributor to the severe anemia that kills almost half of the 2 million people worldwide who die each year of malaria. The culprit is a protein cells make in response to inflammation called MIF, which appears to suppress red blood cell production in people whose red blood cells already are infected by malaria parasites.
The parasite that causes malaria – known as plasmodium – is carried through blood by mosquito bites, and in parts of the world where mosquitoes thrive, millions are infected, most of them by early childhood. Once in the bloodstream, plasmodium invades liver and red blood cells and makes more copies of itself. Eventually, as red cells break and free plasmodium to infect other cells, and as the body’s immune system works to kill infected cells, the total number of red blood cells drops, causing anemia.

But not everyone infected with malaria develops severe, lethal anemia. And there are cases where patients who have been cured of infection still develop severe anemia.

This report provides the rationale for a simple, genetic test to sort out which children may be most susceptible to this lethal complication of malarial infection and to identify treatments targeted to them especially, the study’s authors suggest.

“This is important because in places where malaria is endemic, drug treatment resources are scarce,” says the study’s primary author, Michael A. McDevitt, M.D., Ph.D., an assistant professor of medicine and hematology at the Johns Hopkins School of Medicine.

“There are many difficulties with blood transfusion safety and access in Africa, especially in rural areas where most of the malaria-related deaths occur,” says McDevitt. “That led us to search for a better way to identify those most at risk and a better way to treat the disease,” he says.

The study, published online April 24 in the Journal of Experimental Medicine, adds to a growing amount of evidence that an individual’s unique genetic makeup can affect the prevalence and outcome of diseases, in this case the individual risk of malarial anemia.

A number of human proteins, including MIF (which stands for migration inhibitory factor), were long suspected to cause malarial anemia because they are known to reduce red blood cell counts as part of the body’s normal response to such inflammatory conditions as rheumatoid arthritis or some cancers.

Using immature blood cell precursors grown in a dish, the research team showed that adding MIF to the cells decreases both the final number and maturity of red blood cells. The researchers believe this effect can lead to anemia.

When infected with plasmodium, mice genetically engineered to lack MIF experience less severe anemia and are more likely to survive. Without MIF around to prevent blood cells from maturing, the mice appear better able to maintain their oxygen carrying capacity and don’t lose as much hemoglobin, the protein found in red blood cells responsible for binding to oxygen molecules.

“Demonstrating that MIF clearly contributes to severe anemia suggests new ideas for therapies that can block MIF in malaria patients,” says the study’s senior author, Richard Bucala, M.D., Ph.D., a professor of medicine at Yale University School of Medicine.

The research team also found different versions of “promoter” DNA sequences next to the MIF gene that control how much MIF protein a cell makes in response to infection. One version of the MIF promoter leads to less MIF protein made, while cells containing another version of the MIF promoter make much more MIF protein. Differences in the MIF promoter also have been linked to the severity of other inflammatory diseases.

The researchers continue to collaborate in an effort to develop drugs that might block MIF and treat severe anemia in malaria patients.

The researchers were funded by the National Institutes of Health, the Office of Research on Minority Health, a Howard University General Clinical Research Center grant, and the Department of Medicine at Johns Hopkins.

Authors on the paper are McDevitt, Ganapathy Shanmugasundaram and Jeffrey Keefer of Johns Hopkins; Jianlin Xie and Christine Metz of the Feinstein Institute for Medical Research; Jason Griffith, Aihua Liu, Courtney McDonald, Lin Leng and Bucala of Yale; Philip Thuma of the Macha Malaria Research Institute in Choma, Zambia, a field unit of the Johns Hopkins Bloomberg School of Public Health; Victor Gordeuk of Howard University; Robert Mitchell of the James Graham Brown Cancer Center; and John David of Harvard School of Public Health.

Source: Johns Hopkins Medical Institutions

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Mars Meteorite Similar To Bacteria-etched Earth Rocks

Posted by tumicrobiology on May 12, 2006

A new study of a meteorite that originated from Mars has revealed a series of microscopic tunnels that are similar in size, shape and distribution to tracks left on Earth rocks by feeding bacteria.

And though researchers were unable to extract DNA from the Martian rocks, the finding nonetheless adds intrigue to the search for life beyond Earth.

Results of the study were published in the latest edition of the journal Astrobiology.

Martin Fisk, a professor of marine geology in the College of Oceanic and Atmospheric Sciences at Oregon State University and lead author of the study, said the discovery of the tiny burrows do not confirm that there is life on Mars, nor does the lack of DNA from the meteorite discount the possibility.

“Virtually all of the tunnel marks on Earth rocks that we have examined were the result of bacterial invasion,” Fisk said. “In every instance, we’ve been able to extract DNA from these Earth rocks, but we have not yet been able to do that with the Martian samples.

“There are two possible explanations,” he added. “One is that there is an abiotic way to create those tunnels in rock on Earth, and we just haven’t found it yet. The second possibility is that the tunnels on Martian rocks are indeed biological in nature, but the conditions are such on Mars that the DNA was not preserved.”

More than 30 meteorites that originated on Mars have been identified. These rocks from Mars have a unique chemical signature based on the gases trapped within. These rocks were “blasted off” the planet when Mars was struck by asteroids or comets and eventually these Martian meteorites crossed Earth’s orbit and plummeted to the ground.

One of these is Nakhla, which landed in Egypt in 1911, and provided the source material for Fisk’s study. Scientists have dated the igneous rock fragment from Nakhla – which weighs about 20 pounds – at 1.3 billion years in age. They believe that the rock was exposed to water about 600 million years ago, based on the age of clay found inside the rocks.

“It is commonly believed that water is a necessary ingredient for life,” Fisk said, “so if bacteria laid down the tunnels in the rock when the rock was wet, they may have died 600 million years ago. That may explain why we can’t find DNA – it is an organic compound that can break down.”

Other authors on the paper include Olivia Mason, an OSU graduate student; Radu Popa, of Portland State University; Michael Storrie-Lombardi, of the Kinohi Institute in Pasadena, Calif.; and Edward Vicenci, from the Smithsonian Institution.

Fisk and his colleagues have spent much of the past 15 years studying microbes that can break down igneous rock and live in the obsidian-like volcanic glass. They first identified the bacteria through their signature tunnels then were able to extract DNA from the rock samples – which have been found in such diverse environments on Earth as below the ocean floor, in deserts and on dry mountaintops.

They even found bacteria 4,000 feet below the surface in Hawaii that they reached by drilling through solid rock.

In all of these Earth rock samples that contain tunnels, the biological activity began at a fracture in the rock or the edge of a mineral where the water was present. Igneous rocks are initially sterile because they erupt at temperatures exceeding 1,000 degrees C. – and life cannot establish itself until the rocks cool. Bacteria may be introduced into the rock via dust or water, Fisk pointed out.

“Several types of bacteria are capable of using the chemical energy of rocks as a food source,” he said. “One group of bacteria in particular is capable of getting all of its energy from chemicals alone, and one of the elements they use is iron – which typically comprises 5 to 10 percent of volcanic rock.”

Another group of OSU researchers, led by microbiologist Stephen Giovannoni, has collected rocks from the deep ocean and begun developing cultures to see if they can replicate the rock-eating bacteria. Similar environments usually produce similar strains of bacteria, Fisk said, with variable factors including temperature, pH levels, salt levels, and the presence of oxygen.

The igneous rocks from Mars are similar to many of those found on Earth, and virtually identical to those found in a handful of environments, including a volcanic field found in Canada.

One question the OSU researchers hope to answer is whether the bacteria begin devouring the rock as soon as they are introduced. Such a discovery would help them estimate when water – and possibly life – may have been introduced on Mars.
Source: Oregon State University

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‘Coffee Ring’ Formations Found In Drying Drops Of DNA

Posted by tumicrobiology on May 12, 2006

Coffee drinkers are familiar with the ring-shaped stains that result from spilled drops that have dried, in which the brown stain is not evenly distributed, but instead concentrated at the edge. Now, a team led by Gerard Wong, a professor of materials science and engineering, physics, and bioengineering at the University of Illinois at Urbana-Champaign has found the same “coffee-ring” formation in drying drops of DNA.
To gain insights into the physics behind the ring phenomenon, Wong’s team experimentally studied the dynamics of drying DNA droplets on glass surfaces. They report their findings in a paper accepted for publication in the journal Physical Review Letters, and posted on its Web site.

“As the droplet evaporated, DNA chains were transported outward by water flow to the drop’s perimeter,” Wong said. “At the droplet edge, the DNA became increasingly concentrated and formed a liquid crystal with concentric chain orientations. (Liquid crystals are materials that flow like a liquid, but can align in a preferred direction like a crystalline solid.) During the final stages of drying, stresses propagated from the rim inward through the liquid crystal, creating cracks that formed a periodic zigzag pattern.”

To examine the structure and behavior of the DNA liquid crystal, the researchers used a relatively new imaging technique developed at Kent State University. Called fluorescence confocal polarizing microscopy, the technique imaged the DNA in the drying droplet in three dimensions.

“The DNA alignment parallel to the droplet’s edge was counterintuitive,” Wong said. “We had expected the DNA to extend along the direction of flow, which was mainly in the radial direction. But, instead of resembling the spokes of a bicycle wheel, the transported DNA resembled the rim of a bicycle wheel.”

Since nearly all the DNA is concentrated in a narrow ring with almost no DNA in the rest of the stain, these effects should be accounted for in the design of arrays in which DNA droplets are sequentially deposited onto a glass surface for hybridization studies, the researchers report.

“Without optimization of the wetting conditions, it is possible to miss all the DNA in the ring stain of a dried droplet, resulting in false negatives,” Wong said. “We need to think of strategies to minimize this effect.”

The co-authors of the paper are postdoctoral research associate Ivan Smalyukh, graduate students Olena Zribi and John Butler, and professor Oleg D. Lavrentovich, director of the Liquid Crystal Institute at Kent State.
Source: University of Bristol

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