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Archive for May 6th, 2006

Follow The Nitrogen To Extraterrestrial Life; Narrow Search For Water May Miss Important Clues, Say USC Geobiologists

Posted by tumicrobiology on May 6, 2006

The great search for extraterrestrial life has focused on water at the expense of a crucial element, say geobiologists at the University of Southern

Writing in the Perspectives section of the May 5 issue of Science, four USC researchers propose searching for organic nitrogen as a direct indicator of the presence of life. Nitrogen is essential to the chemistry of living organisms.

Even if NASA were to find water on Mars, its presence only would indicate the possibility of life, said Kenneth Nealson, Wrigley Professor of earth sciences in the USC College of Letters, Arts and Sciences.

“It’s hard to imagine life without water, but it’s easy to imagine water without life,” Nealson said.

The discovery of nitrogen on the Red Planet would be a different story.

“If you found nitrogen in abundance on Mars, you would get extremely excited because it shouldn’t be there,” Nealson said.

The reason has to do with the difference between nitrogen and carbon, the other indispensable organic element.

Unlike carbon, nitrogen is not a major component of rocks and minerals. This means that any substantial organic nitrogen deposits found in the soil of Mars, or of another planet, likely would have resulted from biological activity.

Dimming the hopes of life-on-Mars believers is the makeup of the planet’s atmosphere. The abundant nitrogen in Earth’s atmosphere is constantly replenished through biological activity. Without the ongoing contribution of living systems, the atmosphere slowly would lose its nitrogen.

The extremely low nitrogen content in the Martian atmosphere suggests that biological nitrogen production is close to zero.

However, the authors write, it is possible that life existed on Mars at some hypothetical time when nitrogen filled the atmosphere.

Co-author Douglas Capone, Wrigley Professor of environmental biology in USC College, said NASA should establish a nitrogen detection program alongside its water- seeking effort. He noted that next-generation spacecraft will have advanced sampling capabilities.

“What we’re suggesting here is basically drilling down into geological strata, which they’re going to be doing for water anyway,” Capone said.

“The real smoking gun would be organic nitrogen.”

Said Nealson: “If your goal is to search for life, it would be wise to include nitrogen.”

In their acknowledgments, the authors thanked the students of the Spring 2004 Geobiology & Astrobiology course at USC, with whom Nealson and Capone began their discussion on how to search for life outside earth.

“That’s really what stimulated this [paper],” Nealson said.

The authors also thanked NASA, the Department of Energy and the National Science Foundation for their financial support.

Along with Nealson and Capone, USC graduate student Beverly Flood and former USC Research Professor Radu Popa (now a professor of biology at Portland State University) contributed to the Perspectives paper.
Source: University of Southern California

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The Next Flu Pandemic: When It Happens, Restricting Air Travel Won’t Help

Posted by tumicrobiology on May 6, 2006

Restricting air travel from countries where there is a serious influenza outbreak will do little to hold back the spread of the infection, according to the findings of a study conducted at the UK Health Protection Agency and published in the journal PLoS Medicine.

Sometimes a new type of influeza virus appears that causes an illness that is more serious than is usually the case for flu. This happened, for example, in 1918, when a flu pandemic killed between 20 million and 100 million people. Recently, there have been concerns about the new type of bird (avian) flu. At present the virus responsible does not pass easily from birds to humans, and it does not seem to pass from one human to another. However, the fear is that the virus might change and that human-to-human infection could then be possible. Should all this happen, the changed virus would be a major threat to human health.

With current technology, it would take several months to produce enough vaccine against such a new virus for even a small proportion of the world’s population. By that time, it would probably be too late; the virus would already have spread to most parts of the world.

Health authorities must therefore consider all the methods that might control the spread of the virus. With the increase in international travel that has taken place, the virus could spread more quickly than in previous pandemics. Restrictions on international travel might be considered necessary, particularly travel by air. However, it is important to estimate how useful restrictions on air travel might be in controlling the spread of a flu virus. Travel restrictions are usually unpopular and could themselves be harmful. If they are not effective, resources could be wasted on enforcing them.

Researchers of the Centre for Infections, Health Protection Agency, UK used the techniques of mathematical modelling. In other words, complex calculations were done using information that is already available about how flu viruses spread, particularly information recorded during a worldwide flu outbreak in 1968-1969. Using this information, virtual experiments were carried out by simulating worldwide outbreaks on a computer. The researchers looked at how the virus might spread from one city to another and how travel restrictions might reduce the rate of spread. Their calculations allowed for such factors as the time of the year, the number of air passengers who might travel between the cities, and the fact that some people are more resistant to infection than others.

From the use of their mathematical model, the researchers concluded that restrictions on air travel would achieve very little. This is probably because, compared with some other viruses, the flu virus is transmitted from one person to another very quickly and affects many people. Once a major outbreak was under way, banning flights from affected cities would be effective at significantly delaying worldwide spread only if almost all travel between cities could be stopped almost as soon as an outbreak was detected in each city. It would be more effective to take other measures that would control the spread of the virus locally. These measures could include use of vaccines and antiviral drugs if they were available and effective against the virus.

{Citation: Cooper BS, Pitman RJ, Edmunds WJ, Gay NJ (2006) Delaying the international spread of pandemic influenza. PLoS Med 3(6): e212. (http://dx.doi.org/10.1371/journal.pmed.0030212)}

Source: Public Library of Science

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Stomach Receptor For H. Pylori Discovered

Posted by tumicrobiology on May 6, 2006

Scientists have determined that decay-accelerating factor (DAF), a protein found in epithelial cells in the stomach, acts as a receptor for the bacteria Helicobacter pylori. Blocking this interaction could lead to new drugs that reduce the risk of peptic ulcer disease or gastric cancer. The research appears as the “Paper of the Week” in the May 12 issue of the Journal of Biological Chemistry, an American Society for Biochemistry and Molecular Biology journal.

Helicobacter pylori are spiral shaped bacteria that live in the thick layer of mucus that covers the stomach lining. The bacteria are found everywhere in the world, but are especially prevalent in developing countries, where up to 80% of children and 90% of adults can have laboratory evidence of an H. pylori infection–usually without having any symptoms.

The vast majority of H. pylori in colonized hosts are free-living, but approximately 20% bind to gastric epithelial cells. This binding induces an immune response and alters the morphology and behavior of the epithelial cells due to injection of bacterial proteins into the cells. This interaction can lead to peptic ulcer disease, gastric adenocarcinoma, and non-Hodgkins lymphoma of the stomach.

“Ulcers are a breach in the gastric or duodenal mucosa and gastric adenocarcinoma is one type of cancer of the stomach,” explains senior author Dr. Richard M. Peek, Jr. of the Vanderbilt University School of Medicine. “H. pylori alters acid production and can lead to increased acid outputs which causes peptic ulcer disease. The means through which H. pylori causes gastric cancer are more complex but likely involve alterations in gastric epithelial cell responses that are perturbed within the context of a chronic gastric inflammatory infiltrate, which can persist for decades.”

A membrane-imbedded protein found in the stomach called decay-accelerating factor (DAF) has been shown to function as a receptor for several microbial pathogens. Peek and his colleagues were curious as to whether DAF was also involved in H. pylori adherence. To do this, the researchers measured the number of H. pylori that bound to cells that either expressed or did not express DAF. They found that the bacteria do indeed adhere to cells with DAF. They also discovered that H. pylori induce DAF expression in cultured gastric epithelial cells and that mice lacking DAF develop attenuated stomach inflammation.

“Our results indicate that H. pylori can co-opt a host protein as a receptor and that it can increase expression of this receptor in gastric epithelial cells,” says Peek. “Further, absence of this receptor abolishes the inflammatory response that H. pylori induces in infected mice, suggesting that this receptor mediates H. pylori-induced injury in the stomach.”

These findings suggest that drugs that interfere with DAF binding could be used to prevent or treat peptic ulcer disease or distal gastric adenocarcinoma. These new drugs will be a welcome alternative to the current treatment for H. pylori infections which typically involves taking 3 to 4 medications over a 10 to 14 day period.
Source: American Society for Biochemistry and Molecular Biology

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New Treatment Against Persistent Ulcer-inducing Bacteria Successful

Posted by tumicrobiology on May 6, 2006

For those who suffer from stomach ulcers, the daily routine of breakfast, lunch and dinner can be painful. A common cause of these ulcers, as well as other gastric malignancies, is a bacterium called Helicobacter pylori. For some, this infection can be persistent and difficult to treat.
Many approaches have been taken in an attempt to clear such infections, but with limited or unsuccessful outcomes. In a recent meta-analysis of therapies published in the April issue of The American Journal of Gastroenterology, Levofloxacin-based triple therapy was found to be better tolerated and more effective than bismuth-based quadruple therapy for patients with persistent H. pylori despite previous treatment attempts. Levofloxacin is commonly prescribed to treat such infections as pneumonia, bronchitis and urinary tract infections.

According to author William D. Chey, “Helicobacter pylori is a highly prevalent chronic infection with a worldwide prevalence of nearly 50% and U.S. prevalence of 20-40%.” This bacterial infection is particularly difficult to treat because of its ability to adapt to the harsh environment in the stomach. The bacterium guards itself in the lining of the stomach, which prevents the body’s natural defenses (Killer T Cells) from attacking it.

Levofloxacin-based triple therapy may offer an effective and safe treatment option for patients with persistent H. pylori infection, according to researchers. With so many people living with this infection, it has become increasingly important to achieve effective methods of treatment. Levofloxacin-based therapy may prove to be this method.

This study is published in The American Journal of Gastroenterology.

William D. Chey, MD is Associate Professor, Department of Internal Medicine and Director, Gastrointestinal Physiology Laboratory at the University of Michigan. Dr. Chey is conducting research and has extensively published in the areas of GERD and Helicobacter pylori. Dr Chey is conducting research and has published extensively in the areas of functional bowel disease, GERD, and Helicobacter pylori.
Source: Blackwell Publishing Ltd.

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New Study Reveals Structure Of E. Coli Multidrug Transporter Protein; Could Aid In Fight Against Drug-resistant Bacteria

Posted by tumicrobiology on May 6, 2006

Scientists at The Scripps Research Institute have determined the x-ray structure of EmrD, a multidrug transporter protein from Escherichia coli (E. coli), a common bacteria known to cause several food-borne illnesses. Proteins like EmrD that expel drugs from cells contribute significantly to the continued rise in multidrug resistant bacteria, and the re-emergence of drug-resistant strains of diseases such as tuberculosis that were once thought to have been eradicated.

This new study could potentially help researchers find new ways to avoid the problem of multidrug resistance and enhance the potency of existing drug compounds.

The study is being published in ScienceXpress, an advance online edition of the journal Science, on May 5.

“The development of antibiotics to treat infectious disease is being seriously undermined by the emergence of drug-resistant bacteria,” says Geoffrey A. Chang, Ph.D., a Scripps Research associate professor and a member of the Skaggs Institute for Chemical Biology, who led the study. “Multidrug resistance develops in part through the expulsion of drugs by integral membrane transporters like EmrD. Determining the structure of this transporter will add significantly to our general understanding of the mechanism of drug transport through the cell membrane and provide the structural basis for how these proteins go about selecting specific drugs to expel.”

Multidrug resistant bacterial infections raise the cost of medical treatment and are far more expensive than treating normal infections. Treating drug-resistant tuberculosis, for example, requires so-called second-line drugs if standard treatment fails. According to the Centers for Disease Control, second-line drugs can cost as much as “$33,000 per patient in industrialized countries compared to $84 for first-line drugs.” In addition, the centers noted, second-line drugs need to be taken for longer periods of time-from 18 to 36 months-and may require substantial patient monitoring, making these treatments difficult if not impossible to “be available in many of the resource-poor nations where drug-resistant tuberculosis is emerging.”

EmrD belongs to the Major Facilitator Superfamily, a group of transporters among the most prevalent in microbial genomes. These transporters are distinctive in their ability to recognize and expel a highly diverse range of amphipathic compounds. Amphipathic molecules contain both hydrophobic and hydrophilic groups-molecules that repel or are attracted to water, respectively.

The x-ray structure of the EmrD transporter-determined with data collected at the Stanford University Synchrotron Radiation Laboratory and the Advanced Light Source at the University of California, Berkeley-revealed an interior composed primarily of hydrophobic residues. This finding is consistent with its role of transporting hydrophobic or lipophilic molecules-and similar to the interior of another multidrug transporter, EmrE, which Chang and his colleagues uncovered in a study that was published last year in the journal Science.

This internal cavity is the “most notable difference” between EmrD and most non-Major Facilitator Superfamily multidrug transporters that, the new study noted, typically transport “a relatively narrow range of structurally related” compounds. The hydrophobic residues in the EmrD internal cavity are likely to contribute to the general mechanism transporting various compounds through the cell membrane, and may play “an important role in dictating a level of drug specificity” through a number of molecular interactions.

The study also suggests that EmrD intercepts and binds cyanide m-chlorophenyl hydrazone, a known efflux pump inhibitor, before it reaches the cell cytoplasm. This binding is likely facilitated by hydrophobic interactions within the internal cavity of EmrD. The researchers speculate that cyanide m-chlorophenyl hydrazone is either expelled from the bacterial cell or into the periplasmic space-the space between the outer membrane and the plasma membrane in gram-negative bacteria like E. coli.

“While EmrD and EmrE are completely different proteins from different molecular families,” Chang said, “both are multidrug transporters that help bacteria develop multidrug resistance. Together with MsbA, another MDR structure that our laboratory is studying, this new x-ray structure adds another important view of some general structural features across multi-drug resistant transporter families.”

Other authors of the study include Yong Yin, Xiao He, Paul Szewczyk, and That Nguyen of The Scripps Research Institute.

The study was supported by the National Institutes of Health and the Skaggs Institute for Chemical Biology.
Source: Scripps Research Institute

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We are back again

Posted by tumicrobiology on May 6, 2006

Dear all,
Because of the political instability and the consequences that affected all of us in Nepal and abroad, we could not update our site for a month. Now, were are back.
Let’s be together again.
Cheers
Gaffer, TUMDF

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