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This finding suggests suggests evolutionary biology and virology together can accelerate the discovery of viral-defence mechanisms, according to researchers at Fred Hutchinson Cancer Research Center.

These findings by Julie Kerns, Ph.D., a postdoctoral researcher in the Hutchinson Center’s Basic Science Division, published Jan. 25 in the open-access journal PLoS Genetics, present a striking example by which evolutionary studies can directly lead to biomedically important discoveries in the field of infectious diseases.

The immunity gene, called ZAP, is a key player in a newly discovered branch of antiviral defences in mammals referred to as ‘‘intrinsic immunity.’’ Host proteins like ZAP can target intracellular stages of the viral life cycle to inhibit viral activity. The ZAP gene, first discovered in rats, thwarts a variety of divergent viruses, from retroviruses (like HIV) to alphaviruses (like Sindbis) to filoviruses (like Ebola).

Researchers believe ZAP functions by virtue of its RNAbinding abilities, which recognize specific sequences of the virus and target their viral RNA for destruction. Host-virus interactions are a classic example of genetic conflict in which both entities try to gain an evolutionary advantage over the other. This ‘‘back-and-forth’’ evolution is predicted to result in rapid changes of both host and viral proteins, which
results in an evolutionary signature of positive selection, especially at the direct interaction interface.

“This suggests that we might be able to deduce host-virus conflicts purely by looking at rapidly evolving protein segments,” said Kerns, the lead author of the study, which was conducted in collaboration with senior author Harmit Singh Malik, Ph.D., of the Center’s Basic Sciences Division and also co-author Michael Emerman, Ph.D., of the Center’s Human Biology Division Department.

The researchers found that there has been very little sequence evolution in the RNA-binding domain, which
suggests that human ZAP may be similar to the rat gene in its viral RNA-binding specificity.

Surprisingly, the rapid evolution characteristic of “intrinsic immunity” genes was concentrated in a protein domain that was not even present in the originally discovered rat gene.

The authors found that humans encode two protein versions, or isoforms, from a single ZAP gene: a shorter version similar to the original rat gene and a longer version that possesses a rapidly evolving poly (ADP-ribose) polymerase (PARP)-like domain.

In virological assays, the longer human ZAP protein isoform has higher antiviral activity. Thus, positive selection correctly predicted the more potent antiviral isoform of this protein.

The authors further suggest that ZAP is locked in a conflict with alphaviruses. The discovery of a potential human gene that can restrict alphaviral infection is particularly timely as the mosquito-borne alphavirus, Chikungunya, was responsible for a large epidemic in parts of Southeast Asia in 2006 and is now threatening to invade certain parts of Europe.

The researchers believe that this finding has an enormous implications for the understanding of intrinsic immunity against viruses. This could potentially serve as a guide in the development of antiviral therapeutics.

“We think that a particular alphaviral protein may be playing an evolutionary ‘cat-and-mouse’ game with the ZAP gene,” Malik said. “Identifying this protein could lead to novel ways to tackle diseases caused by alphaviruses.”

Source http://www.fhcrc.org

North Carolina Sea Grant researchers have isolated a new peptide antibiotic from the American oyster that may have implications for managing many diseases in oysters.

The new antimicrobial peptide “American oyster defensin” (AOD) may protect against bacteria in Crassostrea virginica, a species that is native to North Carolina and important economically to Atlantic and Gulf Coast fisheries.

“This peptide may be helpful in selecting disease-resistant oysters for aquaculture and fisheries and may also allow for the development of a test to monitor oyster health,” says Ed Noga, professor at the North Carolina State University College of Veterinary Medicine.

“In recent years, a number of pathogens, especially bacteria and parasites, have devastated American oyster populations.”

The research findings appear in the new (Dec. 30) issue of Biochemical and Biophysical Research Communications.

Pathogens such as dermo (Perkinsus marinus) have caused major decreases in oyster productivity — bacterial pathogens — such as Vibrio vulnificus that can cause a food-borne illness are a human health concern, according to Noga.

This is the first time that researchers have isolated an antimicrobial peptide from any oyster species, he says.

NC State veterinary medicine postdoctoral research associate Jung-Kil Seo, as well as scientists J. Myron Crawford and Kathryn L. Stone of Yale University’s Keck Biotechnology Resource Laboratory, collaborated with Noga on the study.

“The results may be used to better understand the innate immune system of American oysters and to enhance research to protect it from important microbial infections,” according to Noga.

“Further studies are needed to identify sites of synthesis and storage of AOD and determine mechanisms affecting its regulation.”

An unexpected find by a team of University of Georgia scientists suggests that reducing the use of antibiotics on poultry farms will do little, if anything to reduce rates of antibiotic resistant bacteria that have the potential to threaten human health.

Dr. Margie Lee, professor in the UGA College of Veterinary Medicine, and her colleagues have found that chickens raised on antibiotic-free farms and even those raised under pristine laboratory conditions have high levels of bacteria that are resistant to common antibiotics. Her findings, published in the March issue of the journal Applied and Environmental Microbiology, suggest that poultry come to the farm harboring resistant bacteria, possibly acquired as they were developing in their eggs.

“The resistances don’t necessarily come from antibiotic use in the birds that we eat,” Lee said, “so banning antibiotic use on the farm isn’t going to help. You have to put in some work before that.”

Lee and her team sampled droppings from more than 140,000 chickens under four different conditions: 1.) commercial flocks that had been given antibiotics; 2.) commercial flocks that had not been given antibiotics; 3.) flocks raised in a lab that had been given antibiotics; and 4.) flocks raised in a lab that had not been given antibiotics. The researchers examined levels of antibiotic resistance in normal intestinal bacteria that do not cause human illness and – in a companion study published in May in the same journal – also examined levels of drug resistant campylobacter bacteria, a common food-borne cause of diarrhea, cramping and abdominal pain.

They found that even chickens raised in the pristine laboratory conditions had levels of antibiotic resistance levels comparable to what was seen on farms that used antibiotics. Even when the levels were lower, Lee adds, they were still well above the reasonable comfort zone for antibiotic resistance – roughly five to 10 percent.

Seventy-three percent of the bacteria from one flock in the antibiotic-free commercial group were resistant to the drug oxytetracycline, for example, while 90 percent were resistant to the drug in a commercial flock that used antibiotics. Ninety-seven percent were resistant in the experimental flock that was given antibiotics, while forty-seven percent were resistant in the experimental group that was not given antibiotics.

Strikingly, they even found bacteria resistant to streptomycin, a common human antibiotic that is rarely used in poultry and was not used on the farms the researchers studied.

Bacteria swap genes relatively easily, and Lee explained that the concern is that drug resistance genes from bacteria that infect poultry could be passed on to bacteria that cause human illness. With these resistance genes, human bacterial illness could become harder to treat.

These concerns led the European Union to ban the use of antibiotics for growth promotion in chickens in 2006. In 2005, the U.S. Food and Drug Administration banned the use of the drug Baytril (the brand name for enrofloxacin, a fluoroquinolone antibiotic) in poultry, citing concerns that it could lead to resistance in human antibiotics such as Ciprofloxacin, also a fluoroquinolone.

Several advocacy groups are pushing for a more comprehensive animal antibiotic ban in the United States, but Lee said her research plus the evidence from the Baytril ban suggests that approach won’t help.

“They banned Baytril in 2005, and if you look at Baytril resistance in campylobacter now it’s essentially unchanged,” Lee said.

In previous studies, Lee has tried to recreate experimentally conditions that should lead to the swapping of resistance genes among bacteria. Lee said these events – known as the horizontal transfer of genes – do occur, but they may not be as common as initially thought.

What may be driving the antibiotic resistance that Lee has observed in her studies is what’s known as vertical transfer – from parent to child – of bacteria carrying resistance genes. In short, the birds may come to the farm harboring antibiotic resistant bacteria.

“This issue of antibiotic resistance is more complicated than once thought,” Lee said. “These findings suggest that banning antibiotics at the farm level may not be as effective as assumed. We need further studies to identify which management practice would be effective”

Lee stresses that for consumers, the advice on poultry is the same that it’s always been. Cook meat thoroughly and use proper food handling and preparation techniques – washing your hands regularly and keeping other foods away from raw chicken, for example – to minimize the risk of illness.

“All foods have the potential to contain pathogens – all of them,” Lee said. “There’s no substitute for good food handling and preparation.”

The study was funded by grants from the FDA and the United States Department of Agriculture.

The effort to find preserved samples of the 1918 influenza virus has been a pursuit of both historical and medical importance.

The influenza pandemic in 1918 was the most devastating single disease outbreak in modern history, and examining the virus that caused it may help prepare for, and possibly prevent, future pandemics. When the complete sequence of the 1918 virus was published in 2005, it represented a watershed event for influenza researchers worldwide.

An article in the journal Antiviral Therapy, scientists at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, narrate the story of how scientists discovered samples of the 1918 strain in fixed autopsy tissues and in the body of a woman buried in the Alaskan permafrost.

The article places this discovery in the context of decades of research into the cause of pandemic influenza, and the authors detail the strange convergence of events that allowed them to recover and sequence the virus in the first place. Its genetic material is so fragile that it should not have survived for days, let alone decades.

In a mass grave in a remote Inuit village near the town of Brevig Mission, a large Inuit woman lay buried under more than six feet of ice and dirt for more than 75 years. The permafrost plus the woman’s ample fat stores kept the virus in her lungs so well preserved that when a team of scientists exhumed her body in the late 1990s, they could recover enough viral RNA to sequence the 1918 strain in its whole entirety. This remarkable good fortune enabled these scientists to open a window onto a past pandemic. It could also help mankind gain a foothold for preventing a future one.

While America’s food supply is the safest in the world, food poisoning is responsible for approximately 76 million illnesses in the United States each year. In fact, it is estimated that 60% or more of the raw poultry sold today probably has disease-causing bacteria. Anyone eating food contaminated by certain bacteria, parasites, or viruses can get food poisoning. Certain factors such as age and physical condition can make certain people more susceptible to food poisoning than others. Infants, pregnant women, the elderly and people with compromised immune systems are at greatest risk.

For most people in good condition, food poisoning is usually neither long lasting nor life-threatening. However, to less healthy individuals it can become a serious health threat, accounting for approximately 5,000 deaths each year.

The good news is that by taking simple precautionary steps while purchasing, handling, and preparing food you can prevent most cases of food poisoning in the home.

What causes food poisoning? Food poisoning is most commonly caused by bacteria, parasites, or viruses that may be present in the food that you have eaten. You may have heard the names of many of these organisms. They include Escherichia coli (E coli), Campylobacter jejuni, Clostridium botulinum, Shigella, Salmonella, Staphylococcus aureus, Trichinella, and Hepatitis A virus, just to name a few. They can be present in a wide range of food including red meat, poultry, milk and other dairy products, eggs, unpasteurized vegetable juices and ciders, spices, chocolate, seafood, and even water.

These organisms may be present on your food when it is bought or can get into the food, including cooked food, if the food comes into contact with raw meat juices on dirty utensils, cutting boards, or countertops used to prepare contaminated food. That’s why it is important not only to thoroughly cook your food, but to wash your hands, utensils, and countertops, before and after you handle raw foods.

What are the symptoms? Symptoms will vary depending on the type and amount of contaminants eaten. Some people may get ill after ingesting only a small amount of harmful bacteria, while others may remain free of symptoms after eating larger quantities. The most common symptoms of food poisoning include nausea, vomiting, diarrhea, stomach pain (cramps), fever, headache, and fatigue. Symptoms may develop as soon as 30 minutes after eating tainted food, but more commonly do not develop for several days or weeks. Symptoms of viral or parasitic food poisoning may not appear for several weeks, while some toxins in fish may take only a few minutes to cause symptoms.

If you have botulism, you probably will not have a fever and the symptoms may include blurred vision, fatigue, dry mouth and throat.

How food poisoning is diagnosed Food poisoning is often suspected when several people become ill after eating the same meal. To diagnose the cause of the illness, your doctor will need to know the symptoms and what was eaten right before the illness occurred. The doctor may need samples of the food, bowel movements, or vomit. These samples can be tested in a laboratory to determine if the food was contaminated and identify the organism causing the illness.

How is it treated? If the symptoms are severe, the victim should see a doctor or get emergency care. Treatment depends on the severity and cause of the food poisoning. Generally, for mild cases of food poisoning, the doctor will recommend for you to rest, drink fluids to prevent dehydration due to vomiting or diarrhea, and to follow a specific diet. It usually only takes about 1 to 5 days to recover from food poisoning.

If you have botulism, your doctor will prescribe an antitoxin. Other types of food poisoning have no antidote. Antibiotics are usually not helpful in treating food poisoning. Medicine to stop vomiting and stomach cramping may be given.

Prevention is the best approach to avoid food poisoning Most cases of food poisoning can be prevented. Below is a list of a few simple Do’s and Don’ts to help you avoid food-borne illness in the home.

● Do wash your hands, utensils, cutting boards, and countertops between different foods ● Do hrefrigerate or freeze perishables right away (Refrigerator temperature should be 41Ëš F and freezer 0ËšF) ● Do thoroughly cook foods. Cook beef, lamb, and pork to an internal temperature of 160ËšF; whole poultry and thighs to 180ËšF; poultry breasts to 170ËšF, ground chicken or turkey to 165ËšF ● Do hrefrigerate leftover foods as soon as possible; leftovers shouldn’t remain unrefrigerated longer than 2 hours. ● While food shopping, do select frozen foods and perishables such as meat, poultry, and fish last- before checking out ● Do use smooth cutting boards made of hard maple or plastic that are free of cracks and crevices ● Do store raw meats in leak-proof containers or on the bottom of the hrefrigerator to prevent juices from dripping on other foods ● Don’t allow uncooked meats, meat juices, or unwashed fruits and vegetables to come in contact with either cooked or washed foods ● Don’t buy frozen seafood if the packages are open, torn, or crushed on the edges ● Don’t buy food in cans that are bulging or dented, or in jars that are cracked ● Don’t ever buy outdated food. Check the “use by” or “sell by” dates ● Don’t buy unpasteurized milk or dairy products ● Do not buy hrefrigerated or frozen products that are not displayed at the proper temperature ● Do not let small children put foods away unsupervised

More information about this important health subject can be obtained from the following sources: Gateway to Government Food Safety Information www.foodsafety.gov U.S. Food and Drug Administration Center for Food Safety and Applied Nutrition http://vm.cfsan.fda.gov/~dms/wh-food.html Food Safety and Inspection Service United States Department of Agriculture www.fsis.usda.gov/OA/pubs/consumerpubs.htm

Supported as an educational service by Novartis Pharmaceuticals Corporation. This information is not intended for use as medical advice. You should discuss this information with your doctor.

Avaraham Henoch, MD 564 West 160th Street New York, NY 10032 Phone: (212) 740-6400

New Zealand with only a population of 6 million people is a nation of food worriers after a 750 people survey found some interesting data on their views of food and food borne pathogens.

Interestingly, scientists believe people may be anxiously worrying over small issues that pose little risk to their health.

In the phone survey conducted for the New Zealand Food Safety Authority (NZFSA), they found that salmonella was the worst food fear, with 77 per cent being “very concerned” about it.

In addition, an antibiotic in meat was next with 67 per cent and campylobacter with 63 per cent.

But scientist Dr Donald Campbell said people were missing the three biggest threats to life, the amount of salt, fat and sugar in their diet.

Interestingly, people were more concern about eating at local buffets, food halls and ethnic restaurants than food made at home in an unhygienic way.

Campbell, the NZFSA principal adviser of public health, was surprised salmonella was the most feared.

“I would have expected campylobacter to be higher than salmonella,” he said.

Campylobacter had a greater impact on the community than salmonella. There were generally 10 times as many cases of campylobacter in a year than salmonella, said Campbell.

New Zealand had a 15 per cent rise in notified campylobacter cases last year to 15,873, compared with 1335 cases of salmonella.

Both are food-borne illnesses that have been associated with chicken and raw meats, and can cause symptoms of diarrhea, abdominal pain, nausea and headache.

Canterbury medical officer of health Alistair Humphrey put campylobacter high on his list of concerns.

But he said many other bugs lurked in food, including norovirus which causes gastroenteritis’s of which there had been outbreaks in Christchurch.

Antibiotics used in animals for therapeutic purposes and to prevent disease may scare consumers towards vegetarianism, but “the evidence is of it being a very low risk,” Campbell said.

Listeria was a rarer food-borne illness (19 cases nationally last year) but could have devastating consequences, he said. At least half of cases occurred in pregnant women and one in four of their babies have died.

Listeria is linked to deli meats, poultry products, smoked seafood’s, soft cheeses and pre-cooked sausages. However stronger regulations have forced many food manufacturers to comply with strict hygiene.

Participants were more spooked about the use of pesticides in food production and additives.

More than 60 per cent of participants were “very concerned” about their potential effects.

Campbell said these were more “perceived risk” than actual risk, as pesticides and additives were covered by regulations.

The authority commissions the surveys every few years to gauge public feeling and tailor its food safety messages. “We eat at least three times a day, so it matters to us all,” Campbell said.

Genetically modified food greatly concerned 56 per cent of respondents, about the same as in two previous years, whereas a new category, food from cloned animals, worried 54 per cent.

“There is such a small use of genetically modified food. I would not put them as high on the list,” said Campbell.

Food allergies and irradiated food brought up the rear, with 47 per cent and 41 per cent respectively.

A team of scientist have developed a specially tailored viruses could eradicate chronic bacterial infections. When certain bacteria multiply, they produce exo-polysaccharides which lead to biofilms which are nearly impossible to eradicate using conventional antibiotics. Biofilms can be found on medical devices such as catheters.

Boston University biomedical engineers have designed a new, highly effective means of dispersing and killing the bacteria living in biofilms. Led by synthetic biologist James Collins, the team has engineered viruses that attack biofilms on two fronts: by killing the bacteria that live in them, and by dissolving the carbohydrates that hold them together. If such bacteria attacking viruses are proved safe for industrial and clinical use, says Collins, researchers could develop stocks of different kinds of viruses, each tailored to attack a different kind of biofilm.

Collins has designed a virus that can disperse more than 99 percent of the E. coli in a model biofilm. Helen Blackwell a chemist at the University of Wisconsin-Madison, believes that this is an “enormous” achievement: “I haven’t seen anything as effective as this approach.” Collins’s engineered virus is described online in the journal Proceedings of the National Academy of Sciences.

Bacteria living communally in biofilms are one thousand times more resistant to antibiotics than free-swimming bacteria are, says Collins. They are protected by a sticky carbohydrate scaffold called a matrix. The matrix blocks antibiotics and cells from the human immune system, and even provides something like a primitive circulatory system for the bacteria.

In a few cases, including some chronic ear infections in children and chronic lung infections in cystic-fibrosis patients, the tissue harboring a biofilm must simply be cut out. Large doses of antibiotics can usually eradicate these infections, says Blackwell.

But she notes that there is some worry that drug-resistant biofilm infections are becoming more common, and that the use of antibiotics seems to induce biofilm formation.

“One thing I like about Collins’s approach is that it is two-pronged, says Philip Stewart, director of the Center for Biofilm Engineering at Montana State University. “The viruses kill the bacteria, but they also target the biofilm matrix.” Collins’s approach is to select a virus that already targets the bacteria of interest, such as E. coli or Staphylococcus. Then he introduces into the virus a gene for an enzyme that dissolves the main carbohydrate component of the biofilm matrix protecting the bacteria.

There are viruses specialized to infect every bacterial species. These viruses replicate inside bacterial cells, then burst them open, killing the bacteria, and spread to other bacterial cells. But they do not harm animal cells or bacteria other than the kind to which they are targeted.

Naturally occurring viruses can attack biofilms. But Collins showed that giving a virus a gene for dissolving the matrix increased the virus’s effectiveness by 4.5 orders of magnitude.

Collins’s proof-of-concept virus is tailored to a particular type of E. coli biofilm. “There are many species and strains of bacteria out there,” he says, and a single biofilm might support multiple bacterial species and strains. To a lesser degree, there is also some diversity in the components of the biofilm matrix. However, Collins says that because of the increasing speed and falling price of DNA-sequencing and synthesis technologies, it would not be difficult to develop a virus tailored to each kind of biofilm.

Collins’s viral technique appears to overcome some of the problems with chemical techniques. Blackwell, who is designing small molecules to disrupt the bacterial signaling pathways that maintain biofilms, says that delivery of biofilm-disrupting chemicals such as enzymes has been a major hurdle.

The risks of such viruses are unclear, but there is some concern that they might provoke a dangerous immune response. One reason they might not have been widely studied for their potential to treat infection, says Collins, is that antibiotics have been sufficient so far. But with the emergence of multi-drug resistant bacterial strains in hospitals, “a number of companies are looking to viruses,” he says.

For industrial applications where you’re not putting them in someone’s body, these viruses could have a huge impact”. Finding and farming bacteria could change the way we live.

The Food and Drug Administration (FDA) and the USDA have extended GRAS (Generally Recognised as Safe) Approval for LISTEXâ„¢ to all Food Products.

In the fight against Listeria, one of the most dangerous food pathogens, US food processing companies can now apply a novel yet natural tool: LISTEXâ„¢ bacteriophages. The FDA and USDA have approved this
product from The Netherlands as GRAS, based on extensive safety and efficacy data and organoleptics tests confirming that LISTEXâ„¢ is safe and has no impact on taste, smell, colour, and other physical properties of treated products.

Bacteriophages or phage are some of the most abundant micro-organisms on earth. Fresh water and seawater can contain as many as 1 billion phages per ml, while in fresh and processed meat and meat products, more than 100 million viable phages per gram are often present. Phages are harmless to humans, animals and plants, and target only bacterial cells. They are extremely specific in regard to the bacteria they recognize.

The LISTEXâ„¢ bacteriophages target only Listeria bacteria (leaving desirable bacteria in place), and are easy to apply in the environmental areas of the production processes or even within the process.

In October 2006 the FDA had already proclaimed GRAS for LISTEXâ„¢ against Listeria in cheese. The extension to all products susceptible to Listeria, opens the door for the meat and fish industry to apply LISTEXâ„¢.

Earlier this month, the Dutch designated inspection office SKAL confirmed the ‘organic’ status of LISTEX™ under EU law, as a result of which it can be used in the EU in regular and organic products.

EBI Food Safety’s CEO, Mark Offerhaus: “Food Safety now tops the agenda of US food processing companies and consumers, who are insisting on ‘green’ solutions, rather than chemicals. Natural bacteriophages prove to be a unique solution, where increased safety does not come at the expense of product characteristics. US food processors can now benefit from LISTEX™, like their European counterparts.”

According to the World Health Organization (WHO), Listeriosis, the disease caused by Listeria monocytogenes, is one of the most severe food borne infections, with a mortality rate of 30%. It can take weeks after exposure before an infection becomes apparent. The US Food Safety and Inspection Service maintain a zero tolerance policy for the bacterium, which grows at refrigeration temperature and is omnipresent.

The first detailed images of an elusive drug that targets the outer wall of bacteria may provide scientists with enough new information to aid design of novel antibiotics. The drugs are much needed to treat deadly infections initiated by Staphylococcus aureus and other bacterial pathogens.

The research team, led by Natalie Strynadka, a Howard Hughes Medical Institute (HHMI) international research scholar at the University of British Columbia in Vancouver, Canada, published its findings in the March 9, 2007, issue of the journal Science.

“This enzyme is an awesome target for antibiotics. We have a totally new understanding of how the enzyme works and how a very good animal antibiotic inhibits the enzyme”, Dr Strynadka said.

Penicillin and many newer antibiotics work by blocking a piece of the machinery bacteria use to construct their durable outer walls. Without these tough, protective coatings, bacteria die. The enzymatic machinery (known as PBP2) studied by Strynadka’s group has two main parts: One end assembles long sugar fibers; the other end stitches them together with bits of protein to form a sturdy inter-locking mesh shell.

Strynadka’s team has provided a long-awaited look at the portion of the enzyme used in the first step of the biochemical pathway that initiates assembly of the sugar coating. The second step is targeted by penicillin and has been well studied.

Although scientists have spent many years identifying bacterial components whose structural features might have weaknesses that can be exploited by antibiotics, progress in turning up bona fide drug targets has been slow. The cell wall enzymes in particular have tantalized scientists, Strynadka said. “The cell wall has all the hallmarks of a great drug target,” she explained. “It is essential to the survival of all bacteria. The enzymes that create the cell wall are unique to bacteria. And it is accessible; you don’t have to get the
antibiotics into the cell.”

In their structural studies, the researchers focused on Staphylococcus aureus, a notorious human pathogen. An epidemic strain of the bacteria known as methicillin-resistant Staphylococcus aureus is resistant to several common antibiotics, including penicillin and amoxicillin, and is a great cause for concern among hospital infectious disease staff.

Postdoctoral fellow Andrew Lovering, who is first author on the paper, hopes the group’s three-dimensional pictures of the sugar-building enzyme from S. aureus will accelerate the search for an effective weapon against the infamous super bug.

The images produced by Strynadka’s team show the enzyme frozen in place by a powerful antibiotic called moenomycin. Moenomycin has been used for decades in animal feed to promote livestock growth. Bacteria have shown very little evidence of resistance to this antibiotic so far, and scientists think related compounds may be promising candidates for use in humans.

“This enzyme is an awesome target for antibiotics,” said Strynadka. “We have a totally new understanding of how the enzyme works and how a very good animal antibiotic inhibits the enzyme.” Although moenomycin is poorly absorbed by the human body, the new understanding of exactly how it
interferes with bacterial enzyme function should help scientists design modified versions that are more suitable for use in people.

Understanding the structure of this enzyme should also speed up screening and design of new antibiotics, which are in constant demand as microbes continually evolve new ways to evade the drugs that researchers design to thwart them.

The time it takes for bacteria to develop resistance to new antibiotics has been as short as one year for penicillin V and as long as 30 years for vancomycin.

Researchers attempting to solve the structure of this enzyme have struggled to recreate its cellular environment in the laboratory. But after much tinkering with different combinations of detergent, ions, and chemical additives, Strynadka’s team was able to crystallize the enzyme so that it would diffract x-rays into a pattern that would ultimately reveal its natural structure. They then were able to repeat the feat to reveal the crystal structure of the enzyme combined with the animal antibiotic.

Their findings help reveal how the enzyme prepares to assemble the bacteria’s sugar-coating by plucking sugars from a fat-sugar package known as lipid II. The antibiotic, which is another kind of sugar-lipid, probably mimics the lipid II molecule by tucking into a fold in the enzyme and taking up the space needed to bind to lipid II, the researchers believe. “We would like to see the enzyme in a complex with its natural substrates as well as with inhibitors,” Lovering said.

In the meantime, scientists now have the details of its shape and key contact points between enzyme and
antibiotic. The enzyme structure is the first ever solved of a member of a family of enzymes that remove sugars from lipids and attach them to other sugars. This process is used in a wide range of biochemical reactions, including allergic responses and cell signaling in cancer.

Researchers from the University of Sheffield have received joint funding from the Engineering and Physical Science Research Council (EPSRC) and the Ministry of Defence (MoD) to develop an innovative sensor to detect bacteria. The new method will use a polymer which will give a fluorescent signal when it encounters bacteria, allowing scientists to easily identify infected wounds much earlier than using conventional methodologies.

The new technology will be of immediate benefit to healthcare industries in general, as well as those involved in detecting infection in battlefield conditions and bacterial contamination, whether accidental or deliberate.

Currently identifying bacterial infection takes several days and requires swabbing and culturing of bacterial swabs as well as the use of specialist bacteriology laboratory facilities.

By combining polymers, which change shape when they encounter bacteria, and developing a light signal through fluorescence non radiative energy transfer (NRET), the researchers will be able to detect early stages of bacterial contamination.

Being developed by a multi-disciplinary team of researchers from the University’s Departments of Chemistry, Engineering Materials and the Dental School, the sensor will have widespread applications beyond the initial project.

Dr Steve Rimmer from the University’s Department of Chemistry, said: “The project is a great example of progress that can be achieved at the life sciences/physical sciences interface and we hope the project will deliver technology of real importance.”

The multi-disciplinary team will be led by Dr Steve Rimmer of the Department of Chemistry and consists of Dr Linda Swanson (Chemistry) Professor Sheila MacNeil (Engineering Materials) and Dr Ian Douglas (Clinical Dentistry).

The project received £670,000 funding jointly from the Engineering and Physical Science Research Council and the Defence Science and Technology Laboratory - an agency of the Ministry of Defence over three years and started in December 2006.