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Putting bacteria on birth control could stop the spread of drug-resistant microbes, and researchers at the University of North Carolina at Chapel Hill have found a way to do just that.

The team discovered a key weakness in the enzyme that helps “fertile” bacteria swap genes for drug resistance. Drugs called bisphosphonates, widely prescribed for bone loss, block this enzyme and prevent bacteria from spreading antibiotic resistance genes, the research shows. Interfering with the enzyme has the added effect of annihilating antibiotic-resistant bacteria in laboratory cultures. Animal studies of the drugs are now underway.

“Our discoveries may lead to the ability to selectively kill antibiotic-resistant bacteria in patients, and to halt the spread of resistance in clinical settings,” said Matt Redinbo, Ph.D., senior study author and professor of chemistry, biochemistry and biophysics at UNC-Chapel Hill.

The study provides a new weapon in the battle against antibiotic-resistant bacteria, which represent a serious public health problem. In the last decade, almost every type of bacteria has become more resistant to antibiotic treatment. These bugs cause deadly infections that are difficult to treat and expensive to cure.

Every time someone takes an antibiotic, the drug kills the weakest bacteria in the bloodstream. Any bug that has a protective mutation against the antibiotic survives. These drug-resistant microbes quickly accumulate useful mutations and share them with other bacteria through conjugation — the microbe equivalent of mating.

Conjugation starts when two bacteria ‘smoosh’ their membranes together. After each opens a hole in their membrane, one squirts a single strand of DNA to the other. Then the two go on their merry way, one with new genes for traits such as drug resistance. Many highly-drug resistant bacteria rely on an enzyme, called DNA relaxase, to obtain and pass on their resistance genes. A mutation that provides antibiotic resistance can then sweep through a colony as quickly as the latest YouTube hit.

The researchers analyzed relaxase because it plays a crucial role in conjugation. The enzyme starts and stops the movement of DNA between bacteria. “Relaxase is the gatekeeper, and it is also the Achilles’ heel of the resistance process,” Redinbo said.

Led by graduate student Scott Lujan, the team suspected they could block relaxase by searching for vulnerability in a three-dimensional picture of the relaxase protein. Lujan, a biochemistry graduate student in the School of Medicine, confirmed the hunch using x-ray crystallography, which creates nanoscale structural images of the enzyme.

The researchers predicted that the enzyme’s weak link is the spot where it handles DNA. Relaxase must juggle two phosphate-rich DNA strands at the same time. The team suspected a chemical decoy — a phosphate ion — could plug this dual DNA binding site. Redinbo, who has a background in cancer and other disease-related research, realized that bisphosphonates were the right-size decoy.

There are several bisphosphonates on the market; two proved effective. The drugs, called clodronate and etidronate, steal the DNA binding site, preventing relaxase from handling DNA. This wreaks havoc inside E. coli bacteria that are preparing to transfer their genes, the researchers found. Exactly how bisphosphonates destroy each bacterium is still unknown, Redinbo said, but the drugs are potent, wiping out any E. coli carrying relaxase. “That it killed bacteria was a surprise,” he said. By targeting these bacteria, the drugs act like birth control and prevent antibiotic resistance from spreading.

Redinbo, who cautions that the results only apply to E. coli, said further testing will reveal whether bisphosphonates also attack similar species like Acinetobacter baumannii (hospital-acquired pneumonia), Staphylococcus aureus (staph infections) and Burkholderia (lung infections).
“We hope this discovery will help existing antibiotics or offer a new treatment for antibiotic-resistant bacteria,” he said.

The drugs may be most effective at sites where clinicians can best control dosage — on skin and in the gastrointestinal tract, Redinbo said. Other applications may include disinfectants and treatments for farm animals.

Study co-authors, all from UNC-Chapel Hill, include Laura Guogas, Heather Ragonese and Steven Matson. Redinbo is a member of the UNC Lineberger Comprehensive Cancer Center.
Redinbo and his colleagues have filed a patent and formed a small company to further develop the technology.

The study appears online the week of July 9, 2007, in the Proceedings of the National Academy of Sciences. Funding was provided by the National Institutes of Health.

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Hours after we learned that a wave of illnesses near a small meteorite impact in Peru were terrestrial in origin, a newly published study gave us a big reason to be glad: bacteria can be made deadlier by space travel.

NASA astronauts grew salmonella bacteria during an Atlantis space shuttle mission in 2006, and found that it had become three times as deadly to lab mice as its earthbound equivalents.

Why would that happen? Apparently, it wasn’t the near-zero gravity, at least not directly. The researchers, interviewed by The Associated Press, said that while they are not completely certain, they said the best explanation offered so far had to do with a little-known phenomenon called fluid shear.

Here is how Cheryl Nickerson, an associate professor at the Center for Infectious Diseases and Vaccinology at Arizona State University, explained it to The A.P.:

“Being cultured in microgravity means the force of the liquid passing over the cells is low.” The cells “are responding not to microgravity, but indirectly to microgravity in the low fluid shear effects.”

“There are areas in the body which are low shear, such as the gastrointestinal tract, where, obviously, salmonella finds itself,” she went on. “So, it’s clear this is an environment not just relevant to space flight, but to conditions here on Earth, including in the infected host.”

Still, it’s hardly time to start shipping cases of Purell to the International Space Station. Astronauts have long been wary of microbial growth there, especially after a mysterious fungus started eating through the Mir Space Station.

No one got sick, but the problem was bad enough to prompt a Russian scientist to worry that destroying the station over Earth at the end of its service life could “do serious damage to humanity.” They did it anyway in 2001, and his worry proved unfounded.

NASA has a bunch of precautions for shuttle flights, including testing astronauts for infections, filtering the air onboard for microbes, disinfecting the water supply on the vehicle and keeping the ship spic-and-span with antibacterial wipes.

The results of the salmonella-on-the-shuttle experiment are being published today in the Proceedings of the National Academy of Sciences

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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.

Legionella bacteria was discovered during routine testing in part of the water sytem within the prison in Kent. As a response, the area has been evacuated.

Inmates in one wing of Maidstone Prison were moved to other jails, while blood tests on a prison officers proved negative, the Ministry of Justice said.

Dr Mathi Chandrakumar, from Kent Health Protection Unit, said none of the prisoners had been affected, however further checks are still on-going.

The Prison Officers Association (POA) said over 80 inmates were moved to other jails, some as far as Durham.

A POA spokesman said the bacteria was found in the shower system in one wing.

A spokeswoman for the Ministry of Justice said it was a mild strain of the bug and the evacuation was a precaution for the safety of prisoners and staff.

“The prison is working closely with public heath officials, to ensure the full process is carried out appropriately,” she added.

And she said the wing would be cleaned, sanitised and then mothballed for pre-planned refurbishment in January 2008.

Hospital tests were carried out on a prison officer on Saturday, she added.

“The officer was discharged and returned to work the following day. The tests did not indicate that the officer has Legionella disease,” she said.

Victorian wings

Maidstone MP Ann Widdecombe praised prison officers for acting quickly.

She said the problem stemmed from overcrowded jails.

Speaking to BBC Radio Kent, she said: “I’m not terribly surprised by it.

“I think the prison service acted quickly. They warned me when they thought they had a problem.

“It seemed almost to be five minutes later that they said ‘Right, we’re going to take action’, so I think they’ve handled it properly.”

She added: “The problem is, when you’ve got prisons badly overcrowded as they are at the moment, and you are using what are described as Victorian wings, it isn’t always possible to be using simply appropriate accommodation.”

The prison currently holds nearly 600 inmates in four residential wings and one segregation unit.

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Everlasting Distributors, Inc. of Bayonne, NJ, is recalling its Blue Ocean Smoked Indian Sardine Tamban 8oz. packaged frozen products because it has the potential to be contaminated with Clostridium botulinum, a bacterium which produces a life threatening neurotoxin and can cause life-threatening illness or death. Consumers are warned not to use the product even if it does not look or smell spoiled.

Botulism, a potentially fatal form of food poisoning, can cause the following symptoms: general weakness, dizziness, double-vision and trouble with speaking or swallowing. Difficulty in breathing, weakness of other muscles, abdominal distension and constipation may also be common symptoms. People experiencing these problems should seek immediate medical attention.

Blue Ocean Smoked Indian Sardine Tamban was distributed in New York and New Jersey areas and it reached consumers through retail stores.

Blue Ocean Indian Sardine Tamban comes in an uncoded white styropor foam tray and vacuum packed with a clear plastic bag.

The potential for contamination was noted after routing testing.

No illnesses have been reported to date in connection with this problem.

Consumers who have purchased the Blue Ocean Smoked Indian Sardine Tamban 8oz. frozen product are urged to return them to the place of purchase for a full refund. Consumers with questions may contact Everlasting Distributors, Inc. at (201) 823-0800.

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