GENES KEY TO STAPH DISEASE SEVERITY, DRUG RESISTANCE FOUND HITCHHIKING TOGETHER

A new study finds that resistance and virulence can travel together. - BRH

GENES KEY TO STAPH DISEASE SEVERITY, DRUG RESISTANCE FOUND HITCHHIKING TOGETHER

U.S. Department of Health and Human Services
NATIONAL INSTITUTES OF HEALTH NIH News
National Institute of Allergy and Infectious Diseases (NIAID)
For Immediate Release: Friday, July 31, 2009

CONTACT: Ken Pekoc, 301-402-1663

GENES KEY TO STAPH DISEASE SEVERITY, DRUG RESISTANCE FOUND HITCHHIKING TOGETHER

Scientists studying Staphylococcus bacteria, including methicillin-resistant S. aureus (MRSA), have discovered a potent staph toxin responsible for disease severity. They also found the gene for the toxin traveling with a genetic component of Staphylococcus that controls resistance to antibiotics. The study, now online in PLoS Pathogens, shows for the first time that genetic factors that affect Staphylococcus virulence and drug resistance can be transferred from one strain to another in one exchange event.

One of the ways Staphylococcus bacteria become drug-resistant is through horizontal gene transfer, whereby resistance genes move from one bacterium to another. Staph bacteria also can exchange virulence genes using the same mechanism, but this was previously assumed to occur separately from the transfer of antibiotic resistance.

Scientists from the National Institute of Allergy and Infectious Diseases (NIAID), a component of the National Institutes of Health, led the study. They collaborated with researchers at the University of Tubingen in Germany and the University of Medicine and Dentistry of New Jersey.

"The discovery that bundled genes determine virulence and antimicrobial resistance suggests a new research focus for scientists trying to better prevent and treat serious staph infections," says Anthony S. Fauci, M.D., NIAID director.

The research involved more than 100 strains of S. aureus and S. epidermidis, both bacteria found on the skin of most people. In recent decades, these bacteria have become increasingly virulent, often causing severe disease that can be resistant to traditional antibiotics such as methicillin.

The studies were directed by NIAID senior investigator Michael Otto, Ph.D. In 2007, he and his colleagues found that staphylococci secrete toxins of the phenol-soluble modulin (PSM) family that are primarily responsible for attracting and killing human white blood cells called neutrophils. This process is critical for the ability of S. aureus-including community-acquired MRSA-to cause disease.

While screening S. aureus and S. epidermidis strains, Dr. Otto's group noticed that some strains produced one additional, previously unknown PSM toxin. The researchers hypothesized that the toxin was somehow connected to drug resistance. This idea surfaced because the toxin appeared in 10 percent of all MRSA strains and 68 percent of all methicillin-resistant S. epidermidis strains analyzed-whereas the researchers did not find it in strains of S. aureus or S. epidermidis that are sensitive to methicillin.

The research group confirmed its theory by identifying the specific location that encodes the toxin, which was in gene clusters that control drug resistance, known as SCCmec. The group named the new toxin PSM-mec.

"This work represents a previously unknown example of a toxin hitchhiking on staphylococcal mobile genetic elements that are primarily in charge of transferring antibiotic resistance," says Dr. Otto. He adds that the finding "should alert the research community that aggressive, drug-resistant staph can evolve more quickly than we assumed."

The research group is continuing its study of PSM-mec in S. epidermidis, where the toxin is more prevalent. Ultimately, being able to neutralize PSM-mec and other toxins that attack human defenses could lead to new treatments for S. aureus and S. epidermidis disease.

NIAID conducts and supports research-at NIH, throughout the United States, and worldwide-to study the causes of infectious and immune-mediated diseases, and to develop better means of preventing, diagnosing and treating these illnesses. News releases, fact sheets and other NIAID-related materials are available on the NIAID Web site at .

The National Institutes of Health (NIH) -- The Nation's Medical Research Agency -- includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit .

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SPECIES BARRIER MAY PROTECT MACAQUES FROM CHRONIC WASTING DISEASE

More information on a prion disease. Prions still remain controversial as infectious agents among some researchers.

SPECIES BARRIER MAY PROTECT MACAQUES FROM CHRONIC WASTING DISEASE

U.S. Department of Health and Human Services
NATIONAL INSTITUTES OF HEALTH NIH News
National Institute of Allergy and Infectious Diseases (NIAID)
For Immediate Release: Wednesday, July 29, 2009

MEDIA CONTACT: Ken Pekoc, 406-375-9690,

SPECIES BARRIER MAY PROTECT MACAQUES FROM CHRONIC WASTING DISEASE

Data from an ongoing multi-year study suggest that people who consume deer and elk with chronic wasting disease (CWD) may be protected from infection by an inability of the CWD infectious agent to spread to people. The results to date show that 14 cynomolgus macaques exposed orally or intracerebrally to CWD remain healthy and symptom free after more than six years of observation, though the direct relevance to people is not definitive and remains under study. Cynomolgus macaques often are used as research models of human disease because they are very close genetically to humans and are susceptible to several forms of human brain-damaging disease. Thus, it was decided to see whether exposure to CWD could induce disease in the macaques. The study appears online in the journal Emerging Infectious Diseases.

CWD is a type of brain-damaging disease known as a transmissible spongiform encephalopathy (TSE) or prion disease. CWD primarily affects deer, elk, and moose. Other TSE diseases include mad cow disease, or bovine spongiform encephalopathy (BSE) in cattle, scrapie in sheep, and sporadic Creutzfeldt-Jakob disease (CJD) in humans. Humans are not susceptible to sheep scrapie, but BSE appears to have infected about 200 people, primarily in Europe in the 1990s. Those findings provided the rationale for the present CWD-macaque study, which began in 2003.

"We plan to continue this study for at least several more years because, although the risk to macaques so far appears to be low, we know that these diseases can take more than 10 years to develop," says Bruce Chesebro, M.D., chief of the Laboratory of Persistent Viral Diseases at Rocky Mountain Laboratories (RML) in Hamilton, Mont. RML is part of the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH). The RML group is leading the study with collaborators from the Colorado Division of Wildlife; State University of New York Downstate Medical Center; New York State Institute for Basic Research in Developmental Disabilities; American Red Cross; and the University of Wyoming.

The findings by the RML group support published field studies done by others in regions of Colorado and Wyoming where CWD is endemic. Between 1979 and 2001, there were no significant increases in human TSE diseases despite the likelihood that hunters in those areas were exposed to CWD through contact with infected animal tissue and contaminated hunting tools such as knives and saws. Extensive laboratory data also supports a human species barrier against CWD.

Notably, the RML study also included identical testing in squirrel monkeys, which are genetically less similar to humans than macaques. Of 15 squirrel monkeys exposed orally to CWD, two displayed disease symptoms 69 months after infection. Of 13 squirrel monkeys exposed intracerebrally to CWD, 11 displayed symptoms between 33 and 53 months after infection. In symptomatic animals, the presence of the CWD agent was confirmed in brain, spleen and lymph nodes.

The results in squirrel monkeys were not surprising because a study elsewhere in two squirrel monkeys yielded similar results. The study by the RML group was different, however, in that it tested oral exposure to CWD and also studied eight CWD samples from different areas of the country. The results in squirrel monkeys confirmed that disease progression in that species appears consistent with disease progression in deer and elk, where severe weight loss is nearly always present.

"The fact that the squirrel monkeys, like the deer and elk, suffered severe weight loss suggests that chronic wasting disease might affect a common region of the brain in different species," notes Dr. Chesebro.

NIAID conducts and supports research-at NIH, throughout the United States, and worldwide-to study the causes of infectious and immune-mediated diseases, and to develop better means of preventing, diagnosing and treating these illnesses. News releases, fact sheets and other NIAID-related materials are available on the NIAID Web site at .

The National Institutes of Health (NIH) -- The Nation's Medical Research Agency -- includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit .
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REFERENCE: Race B et al. Susceptibilities of nonhuman primates to chronic wasting disease. "Emerging Infectious Diseases." DOI: 10.3201/eid1509.090253.

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