New research involving a team of IFR scientists, funded by BBSRC, has taken the first detailed look at what Salmonella does when it enters a new environment, which could provide clues to finding new ways of reducing transmission through the food chain and preventing human illness.

Bacteria can multiply rapidly, potentially doubling every 20 minutes in ideal conditions. However, this exponential growth phase is preceded by a period known as lag phase, where no increase in cell number is seen.

Lag phase was first described in the 19th Century, and was assumed to be needed by bacteria to prepare to exploit new environmental conditions. Beyond this, surprisingly little was known about lag phase, other than bacteria are metabolically active in this period. But exactly what are bacteria doing physiologically during this period?

To fill in this knowledge gap researchers at IFR, along with colleagues at Campden BRI, a membership-based organisation carrying out research and development for the food and drinks industry, have developed a simple and robust system for studying the biology of Salmonella during lag phase.

In this system, lag phase lasts about two hours, but the cells sense their new environment remarkably quickly, and within four minutes switch on a specific set of genes, including some that control the uptake of specific nutrients.

For example, one nutrient accumulated is phosphate which is needed for many cellular processes, and a gene encoding a phosphate transporter was the most upregulated gene during the first four minutes of lag phase.

The cellular uptake mechanisms for iron were also activated during lag phase, and are needed for key aspects of bacterial metabolism. This increase in iron leads to a short term sensitivity to oxidative damage. Manganese and calcium are also accumulated in lag phase, but are lost from the cell during exponential growth.

This new understanding of Salmonella metabolism during lag phase show how rapidly Salmonella senses favourable conditions and builds up the materials needed for growth. This study was carried out by two BBSRC-CASE studentships, which were partially funded by Campden BRI.

Future research to work out the regulatory mechanisms behind these processes and the switch from lag phase to exponential growth will tell us more about how Salmonella can flourish in different environments, and could point to new ways of controlling its transmission in the food chain.

]]> Thu, 09 FEB 2012 09:07:36 AEST Kathmandu (AFP) Feb 5, 2012 - Health workers in Nepal are to cull thousands of chickens following the discovery of the H5N1 strain of bird flu in the southeastern part of the Himalayan country, officials said Sunday.

"We sent samples for investigation to London after chickens started to die of a mysterious disease in commercial poultry farms," said Ram Krishna Khatiwada, of the government's Directorate of Animal Health.

"We have received the test reports today that confirms infection of bird flu in poultry farms in Khanar and Ithari of the Sunsari district."

Bird flu has also been confirmed in the eastern hills of Panchathar district and the tea-producing area of Ilam, Katiwada told AFP, adding that surveillance of farms was to be stepped up and 4,000 chickens would be killed in the affected areas.

"There has not been infection to humans in the area so far," he added.

"Some have complained of itching and vomiting but that is only panic. We will get the situation under control in one or two days."

Nepal's first reported outbreak of bird flu in poultry was in January 2009 in the eastern part of the country.

The virus reached the capital Kathmandu for the first time in December last year, with health workers culling hundreds of chickens and ducks.

If it spreads to humans, bird flu can cause fever, cough, sore throat, pneumonia, respiratory disease and sometimes death.

]]> Thu, 09 FEB 2012 09:07:36 AEST Hanoi (AFP) Feb 2, 2012 - A woman in southern Vietnam has died after contracting the bird flu virus, health authorities said Thursday, in the country's second human death from the virulent disease in less than a month.

Concerns about avian influenza have risen in the region with China, Cambodia and Indonesia all reporting deaths from the H5N1 virus this year.

Vietnam has culled thousands of birds in affected areas in a bid to contain bird flu outbreaks.

The 26-year-old woman from Soc Trang province in the Mekong delta died on January 28. Tests on the victim after she died confirmed she had contracted the H5N1 virus, the Hanoi-based Preventive Healthcare department said.

"The victim culled and ate sick chicken. There had also been sick and dead poultry around her residence," it said in a report.

On January 11, a duck farmer from the southern Mekong delta province of Hau Giang died from bird flu -- Vietnam's first human death from the disease since April 2010.

According to the World Health Organisation, Vietnam has recorded one of the highest numbers of fatalities from bird flu in southeast Asia, with at least 59 deaths since 2003.

The avian influenza virus has killed more than 330 people around the world, and scientists fear it could mutate into a form readily transmissible between humans, with the potential to cause millions of deaths.

Highlighting those fears, the WHO said last month it was "deeply concerned" about research into whether H5N1 could be made more transmissible between humans after mutant strains were produced in labs.

Two separate research teams -- one in the Netherlands and the other in the United States -- separately found ways to alter the virus so it could pass easily between mammals.

]]> Thu, 09 FEB 2012 09:07:36 AEST Chapel Hill NC (SPX) Feb 02, 2012 - Among medical mysteries baffling many infectious disease experts is exactly how the deadly pneumonic plague bacterium, Yersinia pestis, goes undetected in the first few day of lung infection, often until it's too late for medical treatment.

New research from the University of North Carolina at Chapel Hill School of Medicine has opened a door to the answer. Researchers led by William E. Goldman, PhD, professor and chair of microbiology and immunology at the University of North Carolina at Chapel Hilland a leading authority on Y. pestis, show that the plague bacteria transform the lungs from a nasty place for microbes into a playground for them to flourish.

The research appears online in the Proceedings of the National Academy of Sciences during the week of Monday Jan. 30, 2012.

Goldman notes that most other microbes that infect the lungs trigger an antimicrobial response within a few hours after infection. This early inflammatory response is generally sufficient to eliminate microorganisms with no more than mild respiratory symptoms. Not so with Y. pestis; for about 36 hours, the lungs are "quiet," not inflamed, and symptoms are completely absent.

But in the first 36 hours of infection, plague bacteria are having a field day, growing and reproducing rapidly - 2-fold, 100-fold, 100,000-fold - and all of that without outward disease symptoms or measurable changes in lung tissue.

"And then, rather abruptly, symptoms start to appear," Goldman says. "They progress rapidly to the point where you realize this is not just a cold, this is not just the flu. But by then the disease has progressed too far for effective medical intervention, and death is likely within the next day or two."

And once people have pneumonic plague, the bacteria can spread via respiratory droplets to others who have close contact with them. The U.S. Centers for Disease Control and Prevention notes that during the delay between being exposed to Y. pestis and becoming seriously sick, people could travel over a large area, possibly infecting others, which could make the infection more difficult to control.

"Here's the question we wanted to answer: Is the organism avoiding detection or is it actually suppressing the immune responses of the lung?" Goldman said. "The paper is really about the experiments designed to distinguish between these possibilities. And the answer we found suggests the latter."

In their "co-infection" experiments, the UNC study team mixed together a fully virulent Y. pestis strain and a mutant strain known not to be infectious in that it lacked the components essential for it to be a pathogen. The mix was then given to a single laboratory animal.

"The expectation would be that the virulent strain would do an excellent job of infecting the host. And the non-virulent strain would get killed by the host," Goldman said. "But in our experiments, the non-virulent strain would actually grow very well, almost as well as the virulent strain, and we would see this with any non-virulent strain of Y. pestis."

And then the study team tried other microbes, different lung pathogens and an assortment of random microbes - "including the sort of organisms you inhale all the time and that are disposed of easily by the lungs' standard defense mechanisms. But as long as the virulent bacteria were present, the non-virulent organisms would grow," Goldman said.

"There is no other microbe that does that, no other inhaled organism that in a matter of minutes or hours transforms the lung into such a permissive environment for microbial proliferation," he added.

Goldman points out that not much evolutionary distance exists between Yersinia pestis and its closest ancestor, Yersinia pseudotuberculosis, which causes a much milder disease.

"Our work shows that of these two species, only Y. pestis has the ability to transform the lung into an environment that permits an extended period of unrestricted microbial proliferation with no symptoms. Looking at the genetic differences between these two species may reveal the mechanism responsible for this phenomenon exclusive to Y. pestis, and that may lead to new therapeutic strategies for pneumonic plague."

UNC study coauthors were graduate student Paul A. Price, and Jianping Jin, PhD, of the UNC Center for Bioinformatics.

]]> Thu, 09 FEB 2012 09:07:36 AEST Southampton, UK (SPX) Feb 02, 2012 - Researchers at the University of Southampton, University of Oxford and Retroscreeen Virology Ltd have discovered a series of peptides, found on the internal structures of influenza viruses that could lead to the development of a universal vaccine for influenza, one that gives people immunity against all strains of the disease, including seasonal, avian, and swine flu.

Influenza, an acute viral infection, affects hundreds of thousands of people a year and puts an enormous strain on healthcare providers globally. The last pandemic flu outbreak in the UK - swine flu - was in 2009 when it claimed 457 lives. While previous pandemics have been more serious, there is a heightened risk of more severe pandemics in the future.

The scientific collaboration used a research method known as "Human Viral Challenge Studies", where healthy volunteers are infected with influenza virus, and their immune responses closely monitored in an isolation unit.

These were important to the research, published online in Nature Medicine, as they allowed the healthy volunteers to be held in "sterile" isolation conditions and ensured they had no existing infections. The volunteers were then "challenged" with influenza virus, with blood samples being taken at regular intervals to observe how their immune systems responded to the viral infection.

Researchers discovered that the immune systems produced various types of T-cells (part of the immune system that kills both viral particles, and cells infected with viral particles). Notably, the T-cells responded to peptides associated with the internal structures of the influenza viruses.

Unlike the external structures of influenza virus, that mutates very rapidly and creates a new strain of virus most years, the internal structures change very slowly over a long period of time. These internal structures are found in all strains of influenza virus - thus, a vaccine that targets such peptides may provide immunity against all strains of influenza, including seasonal (yearly), avian (bird), and swine flu, for many years.

A vaccine against these peptides would activate the T-cell immune response - which is able to respond much more rapidly than vaccines that activate an antibody response.

Dr Tom Wilkinson, Senior Lecturer in Respiratory Medicine at the University of Southampton, who led the study, says: "Influenza is a virus that we know has a global impact, and the threat of further pandemics is a real one.

Most influenza vaccines only protect us against known influenza strains by creating antibodies in the blood but the influenza virus has the ability to rapidly change itself and new strains can emerge which rapidly spread across the globe by escaping this immunity.

"We have found that there is an important role for T-cells that recognise the flu virus, which if harnessed could protect against most or even all strains of seasonal and pandemic flu. Through this discovery we hope to improve vaccines for future strains of influenza; and potentially protect against the next pandemic. However there is more to do to translate these findings into new approaches to treatment."

"Current flu vaccines are very good at producing antibodies against flu, but not so good at generating a lasting immunity involving T-cells,' says Professor Sir Andrew McMichael, Director of the Medical Research Council (MRC) Weatherall Institute of Molecular Medicine at Oxford University.

"The big question is: if we had a pandemic involving a much more severe virus than the swine flu we saw, what would we do in the six months it takes to develop an effective vaccine? This study suggests that vaccines stimulating a T-cell response might be an option, but there remains a lot to do to be certain of this approach."

Dr Rob Lambkin Williams, Chief Scientific Officer of Retroscreen, adds, "It is great to see the quality of data produced using the challenge study technique. Knowing that the volunteers were only infected with the viral strains that the research team had introduced, takes the guess work out of such research. The immune response observed in these volunteers was as a direct result of the virus to which they had been exposed. This quality of data will have the potential to rapidly speed up the rate that we are able to create a universal vaccine for influenza."

Retroscreen's Chief Executive Officer, Kym Denny said: "Retroscreen is delighted that our scientists and doctors have been able to work so closely with two leading universities. This work significantly expands our understanding of the immune response to influenza infection; this could be key in the fight against a future pandemic."

Finally, Professor John Oxford, President, Scientific Director and founder of Retroscreen and Professor of Virology at St Bartholomew's and the Royal London Hospital, Queen Mary's School of Medicine and Dentistry said: "Dedicated volunteers in our isolation unit have helped us to open a window into why some people get flu and others do not and even better to formulate a new vaccine."

]]> Thu, 09 FEB 2012 09:07:36 AEST Sydney (AFP) Feb 1, 2012 - Some 24,000 Australian ducks were being destroyed Wednesday after testing positive for a low pathogenic strain of the bird flu virus, an outbreak which has prompted poultry export bans in parts of Asia.

The Australian Chicken Meat Foundation said the outbreak of the strain of avian influenza appeared to be confined to two linked duck farms in the southern state of Victoria and any ban on exports was an over-reaction.

Foundation chief Andreas Dubs said Japan's suspension of all Australian poultry imports and Hong Kong's ban on imports from Victoria would have the biggest impact.

"It is often the case that a country might over-react a little at the first news," he told the Australian Broadcasting Corporation.

"I think that might be the case with Japan, that the initial reaction is to stop everything and hopefully, in due course, a few days, those limitations might be lifted."

Dubs said the outbreak appeared to be isolated and had not affected a chicken farm.

"There's no reason to believe that there are any infections elsewhere," he told AFP, but added that there would be continued surveillance after the virus was picked up during routine testing.

He said while the strain involved posed a potential risk to chickens, it was not a public health or food safety risk.

"There's obviously no danger to humans," he said.

Victoria's deputy premier Peter Ryan said the Australian poultry market had a strong reputation and the outbreak would not have a long-term impact.

"These issues do arise intermittently and I'm sure it will be accommodated sooner than later and we'll be back in the market," he said.

]]> Thu, 09 FEB 2012 09:07:36 AEST Washington (UPI) Jan 31, 2012 - A U.S. biosecurity agency says it asked two scientific journals to censor the publication of research on a flu virus for safety reasons.

The US National Science Advisory Board for Biosecurity made the request to the journals Nature and Science to redact the publication of two papers by research teams who modified avian H5N1 influenza strains to create mutant viruses that can be transmitted efficiently between mammals.

The board, in a statement released Tuesday, said it concluded publishing the work in full would provide information that might allow some persons, organizations or governments to develop similar mammal-adapted influenza viruses for harmful purposes.

"A pandemic, or the deliberate release of a transmissible highly pathogenic influenza A/H5N1 virus, would be an unimaginable catastrophe for which the world is currently inadequately prepared," the NSABB said in its comment.

The NSABB did acknowledge the research holds "clear benefits" and could lead to greater preparedness and potential development of new strategies for disease control.

By recommending the basic results be communicated without methods or details, it said, the benefits to society would be maximized and the risks minimized.

]]> Thu, 09 FEB 2012 09:07:36 AEST East Lansing, MI (SPX) Feb 01, 2012 - In the current issue of Science, researchers at Michigan State University demonstrate how a new virus evolves, which sheds light on how easy it can be for diseases to gain dangerous mutations.

The scientists showed for the first time how the virus called "Lambda" evolved to find a new way to attack host cells, an innovation that took four mutations to accomplish.

This virus infects bacteria, in particular the common E. coli bacterium. Lambda isn't dangerous to humans, but this research demonstrated how viruses evolve complex and potentially deadly new traits, said Justin Meyer, MSU graduate student, who co-authored the paper with Richard Lenski, MSU Hannah Distinguished Professor of Microbiology and Molecular Genetics.

"We were surprised at first to see Lambda evolve this new function, this ability to attack and enter the cell through a new receptor - and it happened so fast," Meyer said. "But when we re-ran the evolution experiment, we saw the same thing happen over and over."

This paper follows recent news that scientists in the United States and the Netherlands produced a deadly version of bird flu. Even though bird flu is a mere five mutations away from becoming transmissible between humans, it's highly unlikely the virus could naturally obtain all of the beneficial mutations all at once.

However, it might evolve sequentially, gaining benefits one-by-one, if conditions are favorable at each step, he added.

Through research conducted at BEACON, MSU's National Science Foundation Center for the Study of Evolution in Action, Meyer and his colleagues' ability to duplicate the results implied that adaptation by natural selection, or survival of the fittest, had an important role in the virus' evolution.

When the genomes of the adaptable virus were sequenced, they always had four mutations in common. The viruses that didn't evolve the new way of entering cells had some of the four mutations but never all four together, said Meyer, who holds the Barnett Rosenberg Fellowship in MSU's College of Natural Science.

"In other words, natural selection promoted the virus' evolution because the mutations helped them use both their old and new attacks," Meyer said. "The finding raises questions of whether the five bird flu mutations may also have multiple functions, and could they evolve naturally?"

Additional authors of the paper include Devin Dobias, former MSU undergraduate (now a graduate student at Washington University in St. Louis), Ryan Quick, MSU undergraduate, Jeff Barrick, a former Lenski lab researcher now on the faculty at the University of Texas, and Joshua Weitz on the faculty at Georgia Tech.

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]]> Thu, 09 FEB 2012 09:07:36 AEST Seattle WA (SPX) Jan 30, 2012 - Using a combination of evolutionary biology and virology, scientists at Fred Hutchinson Cancer Research Center have traced the birth of the ability of some HIV-related viruses to defeat a newly discovered cellular-defense system in primates. The research, led by Michael Emerman, Ph.D., a member of the Hutchinson Center's Human Biology and Basic Sciences Division, and Harmit Malik, Ph.D., a member of the Center's Basic Sciences Division, was published online Jan. 26 ahead of the Feb. 16 print issue of Cell Host and Microbe. The work, which also involved researchers in the Hutchinson Center's Computational Biology Program, hinges on the recently discovered cellular-defense protein called SAMHD1, which protects some key cells of the immune system from infection by HIV-1. The protein likely accomplishes this by reducing the available nucleotides, or DNA building blocks, the virus needs for replicating. In response, some viruses related to HIV-1, such as HIV-2 and some simian immunodeficiency viruses that infect other primates, produce a protein called Vpx that binds to SAMHD1 and targets it for destruction. HIV-1, however, does not encode Vpx, but it does encode a related protein called Vpr. Emerman and colleagues tried to address the question of whether HIV-1 lost the ability to degrade SAMHD1 or whether this ability was gained only in the minority of lentiviruses that encode a Vpx protein. To distinguish between these possibilities, the researchers tested both Vpx as well as the related Vpr proteins from a panel representing all currently known primate lentiviruses for their ability to bind and degrade SAMHD1. When the phylogenetic history, or evolutionary relatedness, between these two viral proteins was mapped on top of their functions, the researchers found that SAMHD1-degrading ability was acquired first by the Vpr protein before the Vpx protein was even "born." This new function occurred only once, in a single evolutionary lineage representing three of eight currently known primate lentivirus types. "This means that the ability of lentiviruses to degrade primate SAMHD1 is a newly acquired trait," Emerman said. "However, HIV-1 does not have the capacity to degrade SAMHD1 because its Vpr gene derived from a lineage of viruses in primates that never evolved to gain this function." The researchers also found that Vpr/Vpx proteins have highly species-specific abilities to degrade primate SAMHD1. Thus, while a lentivirus can degrade SAMHD1 within a single primate species, it cannot bind and degrade the SAMHD1 protein from a more distantly related species. The specificity of the virus for its particular host and the fact that SAMHD1 degradation was an evolutionary novelty among lentiviruses suggests that SAMHD1 from some primates is locked in an "evolutionary arms race" with Vpx/Vpr proteins. Such genetic tugs of war exemplify what is known among evolutionary biologists as the Red Queen Principle, a phrase borrowed from the Red Queen in Lewis Carroll's "Through the Looking Glass" that refers to the paradox of running as fast as you can just to stay in place. "Red Queen conflicts" typically put pressure on both sparring partners to continually evolve new ways to outsmart and overcome each other just to stay in the game. In this case, the host proteins evolve to evade degradation by the newly evolved viral proteins. To assess molecular signatures of these evolutionary arms races, first author Efrem Lim, a graduate student in Emerman's lab, compared the evolutionary rates of SAMHD1 across primate evolution. He found that prior to 23 million years ago, there was very little evidence for rapid evolution of SAMHD1. In contrast, SAMHD1 proteins in Old World monkeys that harbor Vpr/Vpx-containing lentiviruses have evolved rapidly for millions of years. "We have not only recreated the birth of SAMHD1-degrading activity in these viruses but also have captured the immediate evolutionary consequence on the host genes they antagonize," said Malik, an evolutionary geneticist. "While such arms races between viruses and host genomes have been documented previously, this is the first instance where the beginning of the Darwinian arms race has been captured in both viral and primate genomes." Emerman, a virologist, speculates the research may have direct implications for HIV-1 and AIDS. "It is possible that HIV-1 is so pathogenic because it needs to grow rapidly in order to compensate for the lack of the ability to deal with SAMHD1," he said. ]]> Thu, 09 FEB 2012 09:07:36 AEST Denver CO (SPX) Jan 27, 2012 - The parasite that causes malaria is a genetic outlier, which has prevented scientists from discovering the functions of most of its genes. Researchers at National Jewish Health and Yale University School of Medicine have devised a technique to overcome the genetic oddity of Plasmodium falciparum, the major cause of human malaria.

This new approach led them discover a new gene involved in lipid synthesis, and opens the door to further genetic discovery for the entire organism. This should foster a much greater understanding of the parasite, and facilitate discovery of new medications for a disease that infects more than 200 million people and kills nearly 700,000 every year.

"The malarial genome has been a black box. Our technique allows us to open that box, so that we can learn what genes in the most lethal human parasite actually do," said Dennis Voelker, PhD, Professor of Medicine at National Jewish Health and senior author on the paper that appeared in the January 2, 2012 , issue of the Journal of Biological Chemistry. "This could prove tremendously valuable in the fight against a disease that has become increasingly drug-resistant."

The genome of P. falciparum was sequenced in 2002, but the actual functions of many of the organism's genes have remained elusive. One of the primary methods for discovering gene function is to copy a specific gene, insert it into a model organism that is easy to grow, often the yeast Saccharomyces cerevisiae, then draw on the incredible knowledge base about yeast and its abundant genetic variants to discover how that inserted gene changes the organism's biology.

DNA is composed of building blocks with the shorthand designations A,T,C and G. The genome of P. falciparum is odd because it is particularly rich in A's and T's. Because of this A-T-rich nature, P. falciparum genes generally do not function when they are inserted into other organisms. As a result, scientists have been largely stymied when trying to understand the functions of P. falciparum's genes.

It turns out, however, that P. falciparum has a close cousin, P. knowlesi, which shares almost all its genes with P. falciparum, but with fewer A's and T's. As a result, P. knowlesi genes function well when inserted into yeast. Scientists can now insert P knowlesi genes into yeast, discover their function, and then match them to corresponding genes in P. falciparum, which reveals the function of the malarial parasite's genes.

"This technique could lead to an explosion in knowledge about malaria and the parasite that causes it." said Dr. Voelker.

The researchers used the technique to discover a new gene involved in the synthesis of lipids in cell membranes of P. falciparum. The gene, phosphatidylserine decarboxylase, directs the formation of a protein unique to malarial parasites and is a potential therapeutic target. For example, selective disruption of lipid synthesis in P. falciparum, would prevent the organism from making new cell membranes, growing and reproducing in human hosts.

]]> Thu, 09 FEB 2012 09:07:36 AEST Subscribe to our daily selection of space, military, environment and energy newsletters responseText http://visitor.constantcontact.com/manage/optin/ea?v=0016gbbKsaiGSpQFojVO8ZoHw%3D%3D