WHO contemplates reforms after admitting missteps on Ebola

World Health Organization (WHO) Director-General Margaret Chan addresses the media during a special meeting on Ebola in Geneva on Jan. 25, 2015. Photo by Pierre Albouy/REUTERS.

In a special session on Sunday, the World Health Organization debated how to reform itself after acknowledging the organization had botched its response to the 2014 Ebola emergency. 

“The Ebola outbreak revealed some inadequacies and shortcomings in this organization’s administrative, managerial, and technical infrastructures,” WHO Director-General Margaret Chan said. At its headquarters in Geneva, Chan presented a series of proposals aimed at ending the current outbreak, as well as reinforcing preparedness globally and guaranteeing the WHO’s ability to address future large-scale outbreaks. 

She stressed the need to streamline recruitment for emergencies, as the current process is “too slow” and emphasized the need for a “one WHO” approach that employs universal operating procedures and tools for responding to emergencies. According to Chan, the current rules for reporting outbreaks – International Health Regulations (IHR) – created to prevent national health emergencies from becoming global crises, are too thin. But the largest lesson she and others at WHO learned during the outbreak fight was that well-trained, and appropriately paid health care workers, are essential to stemming the spread of disease. 

To date there have been more than 21,000 Ebola cases and over 8,400 deaths. “The volatile microbial world will always deliver surprises, Chan said. “Never again should the world be caught by surprise, unprepared.”

Source: WHO

In mice, vaccine stops urinary tract infections linked to catheters

To adhere to catheters and start urinary tract infections, bacteria extend microscopic fibers with sticky proteins at their ends. Scientists have developed a vaccine that blocks the EbpA protein, visible as a white bulge above, and stops infections in mice. Credit: John Heuser

The most common type of hospital-associated infection may be preventable with a vaccine, new research in mice suggests.

The experimental vaccine, developed by researchers at Washington University School of Medicine in St. Louis, prevented urinary tract infections associated with catheters, the tubes used in hospitals and other care facilities to drain urine from a patient's bladder.

Each day a catheter is present in the urethra and the bladder, the risk of urinary tract infection increases. Nearly every patient who has a catheter for more than 30 days acquires a urinary tract infection. The infections make urination painful and can damage the bladder. If untreated, bacteria can cross into the bloodstream and cause sepsis, a potentially life-threatening complication.

"Catheter-associated urinary tract infections are very common," said first author Ana Lidia Flores-Mireles, PhD, a postdoctoral research associate at the School of Medicine. "Antibiotic resistance is increasing rapidly in the bacteria that cause these infections, so developing new treatments is a priority."

The study is available online Sept. 17 in Science Translational Medicine.

Manufacturers typically coat catheters with antibiotics to reduce the risk of infection. But Flores-Mireles and her colleagues in the laboratory of Scott Hultgren, PhD, showed that inserting catheters into the bladder provokes an inflammatory response that results in the catheter being covered with fibrinogen, a blood-clotting protein.

Fibrinogen shields bacteria from the antibiotics and provides bacteria with a landing pad to adhere to and food to consume as they establish an infection, the research revealed.

"The bacteria use long, thin hairs known as pili to anchor themselves to the fibrinogen, and then they can start to form biofilms, which are slimy coatings on the surface of the catheter composed of many bacteria," said co-author Michael Caparon Jr., PhD, professor of molecular microbiology. "The biofilms protect the bacteria from antibiotics and immune cells, further prevent them from being washed from the body by the flow of urine, and make it possible for bacteria to seed the lining of the bladder with infections."

The urethra and bladder of a mouse are too small to insert a full catheter into, but the scientists showed that surgically implanting a small segment of catheter into the bladder via the urethra increased vulnerability to infection in a similar fashion.

Working with Enterococcus faecalis, a common cause of catheter-associated urinary tract infections, Flores-Mireles showed that a protein on the end of the pili, EbpA, binds to fibrinogen and makes it possible for the bacteria to begin forming biofilms.

When Flores-Mireles prevented the bacteria from making EbpA, they couldn't start infections.

"This protein is like the anchor of a boat," she said. "Without the anchor, the infection is at the mercy of the waves and gets washed away."

Next, the researchers injected the mice with a vaccine containing EbpA. The vaccine caused the animal's immune systems to produce antibodies that blocked EbpA and stopped the infectious process.

The scientists are testing to see if the vaccine helps mice clear established infections of E. faecalis. They also are working to develop a monoclonal antibody that blocks EbpA to prevent catheter-associated infections in the urinary tract and elsewhere in the body.

"We took a closer look at this protein and found that one-half of it is essential for binding to fibrinogen to induce infections," Flores-Mireles said. "The segment of genetic code that makes this part of the protein is also found in the genes of many other bacteria that cause urinary tract infections, so a vaccine, antibody or drug that blocks this part of the protein may help prevent other infections linked to catheters in the urinary tract and in other parts of the body."

Source: Washington University in St. Louis

Cold virus replicates better at cooler temperatures

Artist's rendering of a rhinovirus (stock illustration). Credit: © fotoliaxrender / Fotolia

The common cold virus can reproduce itself more efficiently in the cooler temperatures found inside the nose than at core body temperature, according to a new Yale-led study. This finding may confirm the popular yet contested notion that people are more likely to catch a cold in cool-weather conditions.

Researchers have long known that the most frequent cause of the common cold, the rhinovirus, replicates more readily in the slightly cooler environment of the nasal cavity than in the warmer lungs. However, the focus of prior studies has been on how body temperature influenced the virus as opposed to the immune system, said study senior author and Yale professor of immunobiology Akiko Iwasaki.

To investigate the relationship between temperature and immune response, Iwasaki and an interdisciplinary team of Yale researchers spearheaded by Ellen Foxman, a postdoctoral fellow in Iwasaki's lab, examined the cells taken from the airways of mice. They compared the immune response to rhinovirus when cells were incubated at 37 degrees Celsius, or core body temperature, and at the cooler 33 degrees Celsius. "We found that the innate immune response to the rhinovirus is impaired at the lower body temperature compared to the core body temperature," Iwasaki said.

The study also strongly suggested that the varying temperatures influenced the immune response rather than the virus itself. Researchers observed viral replication in airway cells from mice with genetic deficiencies in the immune system sensors that detect virus and in the antiviral response. They found that with these immune deficiencies, the virus was able to replicate at the higher temperature. "That proves it's not just virus intrinsic, but it's the host's response that's the major contributor," Iwasaki explained.

Although the research was conducted on mouse cells, it offers clues that may benefit people, including the roughly 20% of us who harbor rhinovirus in our noses at any given time. "In general, the lower the temperature, it seems the lower the innate immune response to viruses," noted Iwasaki. In other words, the research may give credence to the old wives' tale that people should keep warm, and even cover their noses, to avoid catching colds.

Yale researchers also hope to apply this insight into how temperature affects immune response to other conditions, such as childhood asthma. While the common cold is no more than a nuisance for many people, it can cause severe breathing problems for children with asthma, noted Foxman. Future research may probe the immune response to rhinovirus-induced asthma.

The study was published in the Proceedings of the National Academy of Sciences.

Source: Yale University

Sniffing-out smell of disease in feces: 'Electronic nose' for rapid detection of Clostridum difficile infection

This image depicts from lef to right Dr Martha Clokie, Professor Andy Ellis and Professor Paul Monks from the University of Leicester with the mass spectrometer. Credit: University of Leicester

A fast-sensitive "electronic-nose" for sniffing the highly infectious bacteria C-diff, that causes diarrhea, temperature and stomach cramps, has been developed by a team at the University of Leicester.

Using a mass spectrometer, the research team has demonstrated that it is possible to identify the unique 'smell' of C-diff which would lead to rapid diagnosis of the condition.

What is more, the Leicester team say it could be possible to identify different strains of the disease simply from their smell -- a chemical fingerprint -- helping medics to target the particular condition.

The research is published on-line in the journal Metabolomics.

Professor Paul Monks, from the Department of Chemistry, said: "The rapid detection and identification of the bug Clostridium difficile (often known as C-diff) is a primary concern in healthcare facilities. Rapid and accurate diagnoses are important to reduce Clostridum difficile infections, as well as to provide the right treatment to infected patients.

"Delayed treatment and inappropriate antibiotics not only cause high morbidity and mortality, but also add costs to the healthcare system through lost bed days. Different strains of C. difficile can cause different symptoms and may need to be treated differently so a test that could determine not only an infection, but what type of infection could lead to new treatment options."

The new published research from the University of Leicester has shown that is possible to 'sniff' the infection for rapid detection of Clostridium difficile. The team have measured the Volatile Organic Compounds (VOCs) given out by different of strains of Clostridium difficile and have shown that many of them have a unique "smell." In particular, different strains show different chemical fingerprints which are detected by a mass spectrometer.

The work was a collaboration between University chemists who developed the "electronic-nose" for sniffing volatiles and a colleague in microbiology who has a large collection of well characterised strains of Clostridium difficile.

The work suggests that the detection of the chemical fingerprint may allow for a rapid means of identifying C. difficile infection, as well as providing markers for the way the different strains grow.

Professor Monks added: "Our approach may lead to a rapid clinical diagnostic test based on the VOCs released from faecal samples of patients infected with C. difficile. We do not underestimate the challenges in sampling and attributing C. difficile VOCs from fecal samples."

Dr Martha Clokie, from the Department of Microbiology and Immunology, added: "Current tests for C. difficile don't generally give strain information -- this test could allow doctors to see what strain was causing the illness and allow doctors to tailor their treatment."

Professor Andy Ellis, from the Department of Chemistry, said: "This work shows great promise. The different strains of C-diff have significantly different chemical fingerprints and with further research we would hope to be able to develop a reliable and almost instantaneous tool for detecting a specific strain, even if present in very small quantities."

Source: University of Leicester

Smelly discovery challenges effectiveness of antimicrobial textiles

University of Alberta textiles scientist Rachel McQueen has found that anti-odor clothing may not be living up to its promise. Credit: University of Alberta

Anti-odour clothing may not be living up to its promise, and an ALES researcher is saying it could all be a matter of how the product was tested.

In two separate experiments, Human Ecology researcher Rachel McQueen and her team found that some antimicrobial textiles were far more effective at performing their advertised tasks in the lab than in testing on humans. In one experiment, the fabrics were designed to help lower the risk of infection; in the second, the fabric was treated with a silver compound, which can be marketed preventing odour in clothing.

"We aren't necessarily seeing the same results in the lab about antimicrobial activity translating into antimicrobial activity when we're wearing them next to our bodies in real life," she said.

The first experiment analyzed the effectiveness of three different textiles coated in antimicrobials triclosan, a zinc pyrithione derivative and a silver chloride-titanium dioxide compound. After putting the fabric on people's arms under plastic film for 24 hours, the silver-chloride titanium dioxide compound hardly eliminated any bacteria. Overall, they found the in vivo -- tested on humans -- results were not comparable with in vitro -- tested in the lab -- results in how they prevented microorganisms from surviving in the textile.

The second test had similar results, and tested whether polyester textiles treated with bioactive concentrations of an antimicrobial silver chloride compound reduced armpit odour and bacterial populations. Although lab testing showed antimicrobial activity, the treated fabrics did not lower odour or bacterial intensity in in vivo testing.

McQueen said that anything from sweat to the proteins in the human body can disrupt the antimicrobial properties of a fabric.

"In reality, when it goes to the point that it gets put on a textile... it may not have the same level of effectiveness as the ones they studied," she said.

McQueen said these findings highlight the importance of in vivo testing, which is less common than in vitro testing, in textile product development. But, because the textiles appear to be effective at reducing bacteria in the lab, she said they may be advertised as being anti-odourous, although they may not necessarily be so when actually worn.

So, for now, McQueen suggests thinking twice before trusting textile's advertised claims.

"It's just a real spectrum to how effective they may truly be. So I'd probably say, from a consumer's point of view, if you're actually buying something that says it's antimicrobial, it may not be," she said. "I think that's important to consider in relation to a lot of claims made about textiles, that is, to be skeptical about the claims marketers make."

McQueen's research was recently published in the International Journal of Clothing Science and Technology.

Source: University of Alberta

Up to 80 million bacteria sealed with a kiss

Couple about to kiss (stock image). As many as 80 million bacteria are transferred during a 10 second kiss, according to research published in the open access journal Microbiome.

As many as 80 million bacteria are transferred during a 10 second kiss, according to research published in the open access journal Microbiome. The study also found that partners who kiss each other at least nine times a day share similar communities of oral bacteria.

The ecosystem of more than 100 trillion microorganisms that live in our bodies -- the microbiome -- is essential for the digestion of food, synthesizing nutrients, and preventing disease. It is shaped by genetics, diet, and age, but also the individuals with whom we interact. With the mouth playing host to more than 700 varieties of bacteria, the oral microbiota also appear to be influenced by those closest to us.

Researchers from Micropia and TNO in the Netherlands studied 21 couples, asking them to fill out questionnaires on their kissing behaviour including their average intimate kiss frequency. They then took swab samples to investigate the composition of their oral microbiota on the tongue and in their saliva.

The results showed that when couples intimately kiss at relatively high frequencies their salivary microbiota become similar. On average it was found that at least nine intimate kisses per day led to couples having significantly shared salivary microbiota.

Lead author Remco Kort, from TNO's Microbiology and Systems Biology department and adviser to the Micropia museum of microbes, said: "Intimate kissing involving full tongue contact and saliva exchange appears to be a courtship behavior unique to humans and is common in over 90% of known cultures. Interestingly, the current explanations for the function of intimate kissing in humans include an important role for the microbiota present in the oral cavity, although to our knowledge, the exact effects of intimate kissing on the oral microbiota have never been studied. We wanted to find out the extent to which partners share their oral microbiota, and it turns out, the more a couple kiss, the more similar they are."

In a controlled kissing experiment to quantify the transfer of bacteria, a member of each of the couples had a probiotic drink containing specific varieties of bacteria including Lactobacillus and Bifidobacteria. After an intimate kiss, the researchers found that the quantity of probiotic bacteria in the receiver's saliva rose threefold, and calculated that in total 80 million bacteria would have been transferred during a 10 second kiss.

The study also suggests an important role for other mechanisms that select oral microbiota, resulting from a shared lifestyle, dietary and personal care habits, and this is especially the case for microbiota on the tongue. The researchers found that while tongue microbiota were more similar among partners than unrelated individuals, their similarity did not change with more frequent kissing, in contrast to the findings on the saliva microbiota.

Commenting on the kissing questionnaire results, the researchers say that an interesting but separate finding was that 74% of the men reported higher intimate kiss frequencies than the women of the same couple. This resulted in a reported average of ten kisses per day from the males, twice that of the female reported average of five per day.

To calculate the number of bacteria transferred in a kiss, the authors relied on average transfer values and a number of assumptions related to bacterial transfer, the kiss contact surface, and the value for average saliva volume.

Source: BioMed Central

Body weight heavily influenced by gut microbes: Genes shape body weight by affecting gut microbes

Body sizes (stock image). New research shows that our genetic makeup influences whether we are fat or thin by shaping which types of microbes thrive in our body. Credit: © olly / Fotolia

Our genetic makeup influences whether we are fat or thin by shaping which types of microbes thrive in our body, according to a study by researchers at King's College London and Cornell University.

By studying pairs of twins at King's Department of Twin Research, researchers identified a specific, little known bacterial family that is highly heritable and more common in individuals with low body weight. This microbe also protected against weight gain when transplanted into mice.

The results, published today in the journal Cell, could pave the way for personalised probiotic therapies that are optimised to reduce the risk of obesity-related diseases based on an individual's genetic make-up.

Previous research has linked both genetic variation and the composition of gut microbes to metabolic disease and obesity. Despite these shared effects, the relationship between human genetic variation and the diversity of gut microbes was presumed to be negligible.

In the study, funded by National Institutes of Health (NIH), researchers sequenced the genes of microbes found in more than 1,000 fecal samples from 416 pairs of twins. The abundances of specific types of microbes were found to be more similar in identical twins, who share 100 per cent of their genes, than in non-identical twins, who share on average only half of the genes that vary between people. These findings demonstrate that genes influence the composition of gut microbes.

The type of bacteria whose abundance was most heavily influenced by host genetics was a recently identified family called 'Christensenellaceae'. Members of this health-promoting bacterial family were more abundant in individuals with a low body weight than in obese individuals. Moreover, mice that were treated with this microbe gained less weight than untreated mice, suggesting that increasing the amounts of this microbe may help to prevent or reduce obesity.

Professor Tim Spector, Head of the Department of Twin Research and Genetic Epidemiology at King's College London, said: 'Our findings show that specific groups of microbes living in our gut could be protective against obesity -- and that their abundance is influenced by our genes. The human microbiome represents an exciting new target for dietary changes and treatments aimed at combating obesity.

'Twins have been incredibly valuable in uncovering these links -- but we now want to promote the use of microbiome testing more widely in the UK through the British Gut Project. This is a crowd-sourcing experiment that allows anyone with an interest in their diet and health to have their personal microbes tested genetically using a simple postal kit and a small donation via our website (www.britishgut.org). We want thousands to join up so we can continue to make major discoveries about the links between our gut and our health.'

Ruth Ley, Associate Professor at Cornell University in the United States, said: 'Up until now, variation in the abundances of gut microbes has been explained by diet, the environment, lifestyle, and health. This is the first study to firmly establish that certain types of gut microbes are heritable -- that their variation across a population is in part due to host genotype variation, not just environmental influences. These results will also help us find new predictors of disease and aid prevention.'

Source: King's College London

The shape of infectious prions

Structural changes were located in the prion protein N-terminus, where a novel reorganization of the beta sheet (in yellow) was observed. In the background, the X-ray diffraction pattern of the crystal composed by the complex prion protein-Nanoboy.

Prions are unique infective agents -- unlike viruses, bacteria, fungi and other parasites, prions do not contain either DNA or RNA. Despite their seemingly simple structure, they can propagate their pathological effects like wildfire, by "infecting" normal proteins. PrPSc (the pathological form of the prion protein) can induce normal prion proteins (PrPC) to acquire the wrong conformation and convert into further disease-causing agents.

"When they are healthy, they look like tiny spheres; when they are malignant, they appear as cubes" stated Giuseppe Legname, principal investigator of the Prion Biology Laboratory at the Scuola Internazionale Superiore di Studi Avanzati (SISSA) in Trieste, when describing prion proteins. Prions are "misfolded" proteins that cause a group of incurable neurodegenerative diseases, including spongiform encephalopathies (for example, mad cow diseases) and Creutzfeldt-Jakob disease. Legname and coworkers have recently published a detailed analysis of the early mechanisms of misfolding. Their research has just been published in the Journal of the American Chemical Society, the most authoritative scientific journal in the field.

"For the first time, our experimental study has investigated the structural elements leading to the disease-causing conversion" explains Legname. "With the help of X-rays, we observed some synthetic prion proteins engineered in our lab by applying a new approach -- we used nanobodies, i.e. small proteins that act as a scaffolding and induce prions to stabilize their structure." Legname and colleagues reported that misfolding originates in a specific part of the protein named "N-terminal." "The prion protein consists of two subunits. The C-terminal has a clearly defined and well-known structure, whereas the unstructured N-terminal is disordered, and still largely unknown. This is the very area where the early prion pathological misfolding occurs" adds Legname. "The looser conformation of the N-terminal likely determines a dynamic structure, which can thus change the protein shape."

"Works like ours are the first, important steps to understand the mechanisms underlying the pathogenic effect of prions" concludes Legname. "Elucidating the misfolding process is essential to the future development of drugs and therapeutic strategies against incurable neurodegenerative diseases."

Source: Sissa Medialab

Targeted culling of deer controls disease with little effect on hunting

A new study found that the targeted culling of deer prevents the rampant spread of chronic wasting disease to healthy deer.

Chronic wasting disease, the deer-equivalent of mad cow disease, has crept across the U.S. landscape from west to east. It appeared first in captive mule deer in Colorado in the late 1960s. By 1981, it had escaped to the wild. It reached the Midwest by 2002. Little is known about its potential to infect humans.

The effort to keep chronic wasting disease in check in Illinois is a success, report researchers Nohra Mateus-Pinilla, left, a wildlife veterinary epidemiologist with the Illinois Natural History Survey; U. of I. animal sciences professor Jan Novakofski; and postdoctoral researcher Michelle Green.

Now researchers at the University of Illinois offer a first look at the long-term effectiveness of the practice of culling deer in areas affected by CWD to keep the disease in check. Their study appears in the journal Preventive Veterinary Medicine.

Each year, the Illinois Department of Natural Resources tests 7,000 (hunted, culled or incidentally killed) deer for CWD infection, conducts aerial surveillance to see where deer congregate and sends in sharpshooters to cull deer at the sites with disease, said Jan Novakofski, a professor of animal sciences at the University of Illinois and an author of the study.

"We know a lot about how far deer typically move," he said. "If they're sick, they're going to spread the disease that far. So if you find a deer that's sick, you draw that small circle and you shoot there."

Novakofski called this approach "a textbook scientific strategy for control. You reduce contact and you reduce the spread of infection with the smallest overall impact on healthy deer."

He and his colleagues at the Illinois Natural History Survey (part of the Prairie Research Institute at the U. of I.) found that the strategy worked: The prevalence of CWD in tested Illinois deer remained at about 1 percent from 2002 to 2012.

The team also found that hunters were killing more deer each year in each region of the state (north, central and south) regardless of CWD and CWD management. Statewide, the number of deer killed by hunters went from 147,830 in 2001, before the appearance of CWD, to 181,451 in 2012. The only exception: Two counties out of 10 with cases of CWD saw a reduction in hunter harvest over the same period.

"We wanted to know whether Illinois hunters have fewer deer to hunt now than they did before CWD," said Nohra Mateus-Pinilla, a wildlife veterinary epidemiologist at the INHS who led the study with postdoctoral researcher Mary Beth Manjerovic. "We found that hunter harvest has increased, and the prevalence of CWD has been maintained at low levels for 10 years in Illinois."

This finding answers a long-time complaint by some hunters that the culling of deer makes it harder for them to find deer to shoot, Novakofski said.
"Since 2001, hunter harvest of deer has increased similarly in the northern region of Illinois, where CWD occurs, and the rest of the state, where there is no disease or sharpshooting," he said.

In the two Illinois counties with fewer deer, "the reductions were 11 to 20 percent," Manjerovic said.

The team compared the Illinois experience with that of Wisconsin, which changed its CWD-management strategy from one that relied on culling to one that consisted primarily of allowing hunters to thin deer herds, the researchers said. Wisconsin saw a striking increase of infection in CWD-tested deer after it did that, the team found.

"In the early years in Wisconsin, (CWD prevalence) was still about 1 percent, just as it was in Illinois," Manjerovic said. "Then the strategy changed. Since 2007, CWD prevalence has increased to about 5 percent."

"We can't find an environmental or other variable that explains the increase in prevalence except a change in management," Novakofski said.

The numbers may not seem alarming to some, said postdoctoral researcher and co-author Michelle Green. But the trend is of concern, she said.

"CWD is a prion disease (like mad cow disease) and it's 100 percent fatal. 
There's no current way that we can actually make the deer better, so it's important that we keep it from spreading too far throughout the population," she said. "And then there's also the connection to mad cow disease. We don't have enough information yet to really understand what the impact to human health could be."

"We all hope that there is never a case of chronic wasting disease in humans. We all hope that it never spreads to people or agricultural animals," Novakofski said. "If it ever does, the investment in maintaining prevalence at a low level in Illinois will be repaid a thousand-fold."

Source: University of Illinois at Urbana-Champaign

Native fungus suggested as another tool for restoring ghostly whitebark pine forests

Siberian slippery jack is a native fungus that may help in the effort to restore whitebark pine forests.
Credit: Cathy Cripps

Cathy Cripps doesn't seem to worry about the grizzly bears and black bears that watch her work, but she is concerned about the ghosts and skeletons she encounters.

The ghosts are whitebark pine forests that have been devastated by mountain pine beetles and white pine blister rust, said the Montana State University scientist who studies fungi that grow in extreme environments. The skeletons are dead trees that no longer shade snow or produce pine cones. The round purple pine cones hold the seeds that feed bears, red squirrels and Clark's nutcracker birds. Shade at the top of watersheds keeps snow from melting too fast in the spring, preventing trout streams from drying up too early in the summer.

Fortunately, she has found hope in a native fungus called Siberian slippery jack, or Suillus sibiricus, said Cripps, a mycologist in MSU's Department of Plant Sciences and Plant Pathology.

Cripps conducted a three-year study in collaboration with Waterton Lakes National Park in Canada that showed a 10 to 15 percent increase in the survival rate of whitebark pine seedlings when Siberian slippery jack spores are injected into the soil around them. The injection takes place in nurseries before the seedlings are transplanted in the mountains.

That increase is significant and good news for those trying to reinstate whitebark pine trees to the north-central Rocky Mountains and Pacific Northwest, Cripps said. The whitebark pine is a keystone species that grows at high elevations where other trees cannot, but it has been declared an endangered species in Canada and awaits the designation in the United States.

"That (jump in survival rates) might not sound like a big difference, but a small amount is a big deal considering the labor-intensive process," Cripps said.

Cyndi Smith, scientist emeritus at Waterton, said "The positive results have encouraged Waterton Lakes National Park to continue inoculating both whitebark and limber pine seedlings, to give them the best opportunity we can to establish and survive to maturity."

Participants in the research project, in addition to Cripps' and Smith's teams, were the U.S. Forest Service, National Park Service and volunteers from the United States and Canada.

Explaining how the collaboration began, Smith said, "Cathy gave a presentation on some of her Yellowstone work at the annual science meeting of the Whitebark Pine Ecosystem Foundation in Hailey, Idaho, in 2006. I was really taken with the idea that the ecosystem may have lost the beneficial fungi because our forests have been dead and dying for so long and that perhaps there was a way to reverse that trend so I approached Cathy with the idea.

"I'm a big believer in collaboration, whether locally or internationally, but certainly working with someone of Cathy's academic stature has been very helpful when I have applied for funding for whitebark and limber pine projects," Smith said, adding that, "Cathy's enthusiasm is very infectious, and it is a delight to work with her."

To carry out the research project, the participants placed cages around whitebark pine trees to collect pine cones without interference from wildlife. Then they tested the cones to see if they were resistant to white pine blister rust, removed seeds by hand from the resistant cones, grew the seeds into seedlings and shipped them to the nursery in Glacier National Park.

Cripps and former graduate student Erin Lonergan drove to Waterton Lakes 

National Park and throughout the Greater Yellowstone area, hiked to the tops of mountains and collected the Siberian slippery jack and other fungi from whitebark pine forests. Then they returned to MSU where they used a coffee grinder to process the spongy outer layer of the fungi. They added water to create a spore slurry, stored the mixture at MSU and later injected about 3 million spores into the soil around each seedling temporarily housed at the Glacier National Park nursery.

A few months later, volunteers planted more than 1,000 seedlings into MSU's test plots. Most of those test plots were located in Waterton, while others were in the neighboring Glacier National Park. The two parks together comprise Waterton-Glacier International Peace Park.

Two years into the study, Lonergan, Cripps and Smith reported success in the journal, American Forests. One year later, they announced their final results in the spring/summer 2014 issue of Nutcracker Notes, a small journal hosted by the Whitebark Pine Ecosystem Foundation.

"We wanted to get the word out that results after three years showed that inoculation with these native fungi significantly improved the survival of rust resistant seedlings, especially when inoculated seedlings were planted in burned areas near shelter objects such as stumps and logs," Cripps said.

High nitrogen fertilizations and fungicides prevent the inoculations from working, Cripps said. The age of the seedlings is important because they need to grow plenty of side roots before being inoculated.

When successful, the injected fungi slip like tiny socks over the ends of every root of the whitebark pine seedling and form a relationship that benefits both the tree and the fungi, Cripps said. The fungi help the seedling take in more nutrients and water from the soil. The tree produces the sugars that feed the fungi.

"Instead of being bad guys, these fungi are beneficial," Cripps said of the Siberian slippery jack. "They help plants take up nitrogen and phosphorus from the soil. That's a big deal."

Her study is one of many research projects involving whitebark pine forests, but it's unique because it focuses on beneficial native fungi, Cripps said. She added that land managers might want to incorporate MSU's findings into their overall strategy for restoring whitebark pine forests. She noted that large-scale inoculations are already planned for nurseries in Canada. She said inoculating beneficial fungi into nursery stock is common in Europe.

"As we work to save the vital whitebark pine from disappearing from the landscape, it is essential to use all available tools," Cripps said. "Ectomycorrhizal fungi are an integral part of forest integrity, ecology and health. Showing respect for these mighty microbes might just mean the difference between the restoration and death of a forest."

"Ectomycorrhizal fungi" refers to beneficial fungi that form a symbiotic relationship with the roots of trees. Siberian slippery jack is one of those fungi, and it only associates with five-needle pines. White pine blister rust is another type of fungus, one of the "bad guys."

Source: Montana State University

Bacteria could be rich source for making terpenes

Odoriferous terpene metabolites: A phylogenetic tree of terpene synthases shows the synthases (bold face or underlined) found by researchers in Japan and at Brown University using bacterial sequences. Credit: Image courtesy of Brown University

If you've ever enjoyed the scent of a pine forest or sniffed a freshly cut basil leaf, then you're familiar with terpenes. The compounds are responsible for the essential oils of plants and the resins of trees. Since the discovery of terpenes more than 150 years ago, scientists have isolated some 50,000 different terpene compounds derived from plants and fungi. Bacteria and other microorganisms are known to make terpenes too, but they've received much less study.

New research at Brown University, published in the Proceedings of the National Academy of Sciences, shows that the genetic capacity of bacteria to make terpenes is widespread. 

Using a specialized technique to sift through genomic databases for a variety of bacteria, the researchers found 262 gene sequences that likely code for terpene synthases -- enzymes that catalyze the production terpenes. The researchers then used several of those enzymes to isolate 13 previously unidentified bacterial terpenes.

The findings suggest that bacteria "represent a fertile source for discovery of new natural products," the researchers write.

David Cane, a professor of chemistry at Brown and one of the authors on the new paper, began working about 15 years ago to understand how bacteria make terpenes.

"At that time, the first genomic sequences of certain classes of bacteria were just beginning to come out," he said. "We had this idea that maybe you could find the enzymes responsible for making terpenes by looking at the sequences of the genes that were being discovered."

To do that, Cane searched through the genome data gathered for a group of bacteria called Streptomyces, looking for sequences similar those known to produce terpene synthases in plants and fungi. Eventually, he found that Streptomyces did indeed have genes encoding terpene synthases and that those enzymes could be used to make terpenes.

The verified bacterial sequences found by Cane and others enabled researchers to refine subsequent searches for additional terpene synthase genes. "Instead of using plant sequences or fungal sequences as your search query, we can now use bacterial sequences, which should yield a greater degree of similarity," he said. "So now we're fishing in the right waters with the right kind of bait, and you can find more matches."

This latest paper made use of the third generation of iterative searches and a powerful search technique developed by Haruo Ikeda of Kitasato University in Japan. Previous work had identified 140 probable sequences for terpene synthases. This latest work expanded that to 262.

The next step was to verify that these sequences did indeed code for enzymes capable of making terpenes. Testing all 262 wasn't practical, so the team chose a few they thought might give them the best chance of finding terpene compounds that hadn't previously been identified. They looked for sequences that didn't seem to fit clearly into previously known categories of terpenes.

After they had selected a few, the team made use of a genetically engineered Streptomyces bacterium as a bio-refinery to generate the terpene products.

"What Professor Ikeda did, in collaboration with us, is develop a variant of a very well-studied Streptomyces system," Cane said. "He eliminated the genes that were responsible for making most of its native products, but he left behind all of the capacity to provide the starting materials and handle the accumulation of products."

By taking some of the gene sequences they found and splicing them into their test organism, the researchers could let the organisms generate the product using the instructions from the newly introduced gene. Using this method, they were able to make 13 previously unknown terpenes, their structures verified by mass spectrometry and nuclear magnetic resonance spectroscopy.

"It's a big step forward in the area in that it provides a paradigm for how one could go about discovering many new substances," Cane said. "It's a good example of how one can use sequence analysis to identify genes of interest and then apply molecular genetic and microbiological techniques to produce the chemical substances of interest."

The work also suggests that there may be many new terpene products as yet undiscovered hiding in the genomes of bacteria.

Source: Brown University

Scrapie could breach the species barrier

Scrapie is a neurodegenerative disease that has been known for centuries and which affects sheep and goats. Credit: INRA/Florent Giffard

INRA scientists have shown for the first time that the pathogens responsible for scrapie in small ruminants (prions) have the potential to convert the human prion protein from a healthy state to a pathological state. In mice models reproducing the human species barrier, this prion induces a disease similar to Creutzfeldt-Jakob disease. These primary results published in Nature Communications on 16 December 2014, stress the necessity to reassess the transmission of this disease to humans.

Scrapie is a neurodegenerative disease that has been known for centuries and which affects sheep and goats. Similar to Bovine Spongiform Encephalopathy (BSE) or mad cow disease, scrapie is caused by a transmissible pathogen protein called prion.

However, and contrary to BSE[1], epidemiological studies have never been able to establish a link between this disease and the occurrence of prion diseases in humans. "Risks of transmitting scrapie to humans (zoonose) were hitherto considered negligible because of the species barrier that naturally prevents prion propagation between species," said Olivier 

Andreoletti, INRA scientist who led the present study.

Researchers at INRA studied the permeability of the human transmission barrier to pathogens responsible for scrapie, using animal models specifically developed for this purpose. This approach previously allowed the confirmation of the zoonotic nature of prions responsible for BSE in cows and of the variant of Creutzfeldt-Jakob disease in humans (vCJD).

Unexpectedly, in these rodent models, certain pathogens responsible for scrapie were able to cross the transmission barrier. Moreover, the pathogens that propagated through this barrier were undistinguishable from the prions causing the sporadic form of Creutzfeldt-Jakob disease (sCJD). This data suggest a potential link between the occurrence of certain sCJD and these animal prions.

"Since CJD is scarce, about 1 case per million and per year, and incubation periods are usually long -several decades- it is extremely difficult for epidemiological studies to try and make this link," explains Olivier Andreoletti.

In their conclusions, the authors stress the fact that CJD cases are rare though scrapie has been circulating for centuries in small ruminants for which we eat the meat. Even if in future studies scrapie is finally confirmed to have a zoonotic potential, the authors consider that this disease does not constitute a new major risk for public health.

Source: INRA-France

Role of microbes, effect on infectious disease dynamics

In the field, UCSB graduate student Andrea Jani uses a sterile swab to sample mucus on the skin of a frog. Frogs are released unharmed after sampling. Credit: Abby Mayer

The adult human body is made up of about 37 trillion cells. Microbes, mainly bacteria, outnumber body cells by 10 to 1. Increasingly, scientists recognize that this huge community of microbes, called the microbiome, affects the health, development and evolution of all multicellular organisms, including humans.

Studies show symbiotic microbes can help prevent infection by disease-causing pathogens. But sometimes the interaction goes the other way, with a pathogen or disease disrupting the normal community of symbiotic bacteria. In a new study, a team of scientists from UC Santa Barbara demonstrates that a fungal pathogen of amphibians does just that. The findings appear today in the Early Edition of the Proceedings of the National Academy of Science.

Landmark experiments with model organisms such as mice have shown that infectious pathogens can disrupt the "normal" microbiome, but the extent to which this process shapes symbiotic microbial communities during disease outbreaks in nature is largely unknown. This new work, conducted by Andrea Jani, a UCSB graduate student in Cherie Briggs' lab in the Department of Ecology, Evolution and Marine Biology (EEMB), addresses a fundamental gap in disease ecology and microbiome research.

Co-authors Jani and Briggs -- also affiliated with UCSB's Biomolecular Science and Engineering program -- found that the chytrid fungus Batrachochytrium dendrobatidis (Bd) appears to drive dramatic changes in symbiotic bacterial communities during natural disease episodes in four populations of the endangered Sierra Nevada yellow-legged frog (Rana sierrae). Chytridiomycosis, an emerging infectious disease of amphibian skin caused by the Bd pathogen, is a leading cause of amphibian biodiversity loss worldwide.

"In the California Sierra Nevada, this disease has led to the rapid extirpation of frogs from hundreds of high-elevation lakes; however, in other lakes, infected frogs of the same species are surviving and persisting with the fungus," explained Briggs, who is the Duncan and Suzanne Mellichamp Chair in Systems Biology. "Given that amphibian skin is the organ infected by Bd, there has been a lot of interest in how antifungal properties of some skin-associated bacteria may protect frogs against this fungal pathogen. In this study we focused on the flip side of this interaction -- that is, how infection with Bd can disrupt the skin microbial community."

"We used next-generation DNA sequencing to document significant shifts in skin-associated bacterial communities of the Sierra Nevada yellow-legged frog during natural Bd outbreaks," Jani explained. "We paired these field surveys with a laboratory infection experiment, demonstrating a causal relationship in which Bd alters the Rana sierrae microbiome."

The researchers found a remarkable consistency in the response of the microbiome to Bd infection among field populations and between the field and laboratory. Several key taxa -- a group of one or more populations of an organism or organisms -- consistently responded in the same direction to Bd infection, suggesting some predictability in the effect of Bd on the microbiome.

"What we found was that the severity of infection with Bd is strongly correlated with the composition of bacterial communities on the skin of frogs," Jani continued. "What was surprising was that across the different frog populations there was pretty striking consistency in this correlation with Bd. One of the frog populations crashed due to Bd infection; the other three populations seemed to tolerate Bd infections. So there are different disease dynamics going on, yet they have a similar relationship between the microbiome and Bd."

Still, the underlying mechanism for Bd-induced changes in the microbiome is not clear. The researchers hypothesize that the pathogen might compete directly with certain bacteria for space or resources or release compounds that negatively or positively affect certain bacterial species. Alternatively, they say, some pathogens could control immune responses of the host to favor their own growth and disrupt the normal symbiotic bacterial community.

Jani noted that some promise exists for probiotic treatments as a tool to fight the decline of frogs due to Bd, but she was careful to qualify that statement by saying that there is still a lot that scientists do not understand about either the environmental impact that might have or what the interactions are between the natural bacteria that exist on frogs and the pathogen. "We find that some taxa previously identified as having anti-Bd properties are driven to low abundances by Bd infection, which may limit their effectiveness as probiotic agents," she said.

"This study shows the importance of knowing how the many benign microbes living on and in our bodies interact with those that cause disease," said Sam Scheiner, National Science Foundation (NSF) director for the joint NSF/National Institutes of Health/United States Department of Agriculture Ecology and Evolution of Infectious Disease Program, which funded the research. "The results are important for developing responses to a disease causing amphibians to go extinct worldwide and also have implications for future studies of human health.

Source:  University of California - Santa Barbara

Experimental Ebola vaccine appears safe, prompts immune response

A 39-year-old woman, the first participant enrolled in VRC 207, receives a dose of the investigational NIAID/GSK Ebola vaccine at the NIH Clinical Center in Bethesda, Md. on September 2. Credit: NIAID

An experimental vaccine to prevent Ebola virus disease was well-tolerated and produced immune system responses in all 20 healthy adults who received it in a Phase 1 clinical trial conducted by researchers from the National Institutes of Health. The candidate vaccine, which was co-developed by the NIH's National Institute of Allergy and Infectious Diseases (NIAID) and GlaxoSmithKline (GSK), was tested at the NIH Clinical Center in Bethesda, Maryland. The interim results are reported online in advance of print in the New England Journal of Medicine.

"The unprecedented scale of the current Ebola outbreak in West Africa has intensified efforts to develop safe and effective vaccines, which may play a role in bringing this epidemic to an end and undoubtedly will be critically important in preventing future large outbreaks," said NIAID Director Anthony S. Fauci, M.D. "Based on these positive results from the first human trial of this candidate vaccine, we are continuing our accelerated plan for larger trials to determine if the vaccine is efficacious in preventing Ebola infection."

The candidate NIAID/GSK Ebola vaccine was developed collaboratively by scientists at the NIAID Vaccine Research Center (VRC) and at Okairos, a biotechnology company acquired by GSK. It contains segments of Ebola virus genetic material from two virus species, Sudan and Zaire. The Ebola virus genetic material is delivered by a carrier virus (chimpanzee-derived adenovirus 3 or cAd 3) that causes a common cold in chimpanzees but causes no illness in humans. The candidate vaccine does not contain Ebola virus and cannot cause Ebola virus disease.

The trial enrolled volunteers between the ages of 18 and 50. Ten volunteers received an intramuscular injection of vaccine at a lower dose and 10 received the same vaccine at a higher dose. At two weeks and four weeks following vaccination, the researchers tested the volunteers' blood to determine if anti-Ebola antibodies were generated. All 20 volunteers developed such antibodies within four weeks of receiving the vaccine. Antibody levels were higher in those who received the higher dose vaccine.

The investigators also analyzed the research participants' blood to learn whether the vaccine prompted production of immune system cells called T cells. A recent study by VRC scientist Nancy J. Sullivan, Ph.D., and colleagues showed that non-human primates inoculated with the candidate NIAID/GSK vaccine developed both antibody and T-cell responses, and that these were sufficient to protect vaccinated animals from disease when they were later exposed to high levels of Ebola virus.

The experimental NIAID/GSK vaccine did induce a T-cell response in many of the volunteers, including production of CD8 T cells, which may be an important part of immune protection against Ebola viruses. Four weeks after vaccination, CD8 T cells were detected in two volunteers who had received the lower dose vaccine and in seven of those who had received the higher dose.

"We know from previous studies in non-human primates that CD8 T cells played a crucial role in protecting animals that had been vaccinated with this NIAID/GSK vaccine and then exposed to otherwise lethal amounts of Ebola virus," said Julie E. Ledgerwood, D.O., a VRC researcher and the trial's principal investigator. "The size and quality of the CD8 T cell response we saw in this trial are similar to that observed in non-human primates vaccinated with the candidate vaccine."

There were no serious adverse effects observed in any of the volunteers, although two people who received the higher dose vaccine did develop a briefly lasting fever within a day of vaccination.

Source: NIH/National Institute of Allergy and Infectious Diseases

Microbiologists discover how gut bacterial resources are hijacked to promote intestinal, foodborne illnesses

Dr. Vanessa Sperandio. Credit: Image courtesy of UT Southwestern Medical Center

UT Southwestern Medical Center microbiologists have identified key bacteria in the gut whose resources are hijacked to spread harmful foodborne E. coli infections and other intestinal illnesses.

Though many E. coli bacteria are harmless and critical to gut health, some E. coli species are harmful and can be spread through contaminated food and water, causing diarrhea and other intestinal illnesses. Among them is enterohemorrhagic E. coli or EHEC, one of the most common foodborne pathogens linked with outbreaks featured in the news, including the multistate outbreaks tied to raw sprouts and ground beef in 2014.

The UT Southwestern team discovered that EHEC uses a common gut bacterium called Bacteroides thetaiotaomicron to worsen EHEC infection. B. thetaiotaomicron is a predominant species in the gut's microbiota, which consists of tens of trillions of microorganisms used to digest food, produce vitamins, and provide a barrier against harmful microorganisms.

"EHEC has learned to how to steal scarce resources that are made by other species in the microbiota for its own survival in the gut," said lead author Dr. Meredith Curtis, Postdoctoral Researcher at UT Southwestern.

The research team found that B. thetaiotaomicron causes changes in the environment that promote EHEC infection, in part by enhancing EHEC colonization, according to the paper, appearing in the journal Cell Host Microbe.

"We usually think of our microbiota as a resistance barrier for pathogen colonization, but some crafty pathogens have learned how to capitalize on this role," said Dr. Vanessa Sperandio, Professor of Microbiology and Biochemistry at UT Southwestern and senior author.

EHEC senses changes in sugar concentrations brought about by B. thetaiotaomicron and uses this information to turn on virulence genes that help the infection colonize the gut, thwart recognition and killing by the host immune system, and obtain enough nutrients to survive. The group observed a similar pattern when mice were infected with their equivalent of EHEC, the gut bacterium Citrobacter rodentium. Mice whose gut microbiota consisted solely of B. thetaiotaomicron were more susceptible to infection than those that had no gut microbiota. Once again, the research group saw that B. thetaiotaomicron caused changes in the environment that promoted C. rodentium infection.

"This study opens up the door to understand how different microbiota composition among hosts may impact the course and outcome of an infection," said Dr. Sperandio, whose lab studies how bacteria recognize the host and how this recognition might be exploited to interfere with bacterial infections. "We are testing the idea that differential gastrointestinal microbiota compositions play an important role in determining why, in an EHEC outbreak, some people only have mild diarrhea, others have bloody diarrhea and some progress to hemolytic uremic syndrome, even though all are infected with the same strain of the pathogen."

The Centers for Diseases Control and Prevention (CDC) estimates that each year roughly 1 in 6 Americans (or 48 million people) gets food poisoning; 128,000 are hospitalized;, and 3,000 die of their food-borne disease. EHEC, which also caused a widespread outbreak in Europe in 2011, can lead to bloody diarrhea, hemorrhagic colitis, and hemolytic uremic syndrome, which in turn can lead to kidney disease and failure. EHEC is among the top five pathogens contributing to domestically acquired foodborne illnesses resulting in hospitalization, according to the CDC. Outbreaks in 2014 were reported in California, Idaho, Massachusetts, Michigan, Missouri, Ohio, Montana, Utah, and Washington.

Source: UT Southwestern Medical Center