PRESS RELEASE: Scientists Identify Factor Key to Severity of Community-Associated Methicillin-Resistant Staph Infections

Maureen Martino — Tue, 13 Nov 2007 09:44:23 -0500

Scientists Identify Factor Key to Severity of Community-Associated Methicillin-Resistant Staph Infections

Newly described proteins in drug-resistant strains of the Staphylococcus aureus bacterium attract and then destroy protective human white blood cells—a key process ensuring that S. aureus survives and causes severe disease, according to scientists at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.

S. aureus disease is a global public health concern because some strains, including community-associated methicillin resistant S. aureus (CA-MRSA), have developed resistance to existing antibiotics. The NIAID scientists hope to use this finding to advance development of new therapeutic treatments.

In a study published online in Nature Medicine, Michael Otto, Ph.D., and his colleagues at NIAID’s Rocky Mountain Laboratories (RML) describe how novel members of the phenol-soluble modulin (PSM) protein family help determine disease severity and eliminate immune defense mechanisms against CA-MRSA.

“This elegant work helps reveal the complex strategy that S. aureus has developed to evade our normal immune defenses,” says Anthony S. Fauci, M.D., NIAID director. “Understanding what makes the infections caused by these new strains so severe and developing new drugs to treat them are urgent public health priorities.”

Up until a year ago, most scientists studying S. aureus believed they had narrowed their search for the cause of severe CA-MRSA infections, focusing on the Panton-Valentine leukocidin (PVL) toxin produced by certain strains. But then last year, Dr. Otto and his RML colleagues published a study indicating that PVL does not play a major role in CA-MRSA infections (see related News Release).

Given the scope of the problem in the United States, Dr. Otto’s group continued its search to understand why the CA-MRSA strains cause widespread and often severe infections in otherwise healthy people. Until now, no one had examined what role PSMs have in Staphylococcus infection.

The RML group identified previously unknown PSMs secreted by S. aureus and identified the genes that encode those PSM proteins. They then compared PSM production between CA-MRSA and the most prominent hospital-associated MRSA strains. The research team found PSM genes in all MRSA strains, but production of the proteins was typically higher in CA-MRSA strains known for severe virulence, according to Dr. Otto.

To determine whether PSMs contribute to virulence, the scientists developed test strains using the most widespread isolates of CA-MRSA, called USA300 and USA400. Each test strain had a certain combination of PSM-encoding genes removed so the researchers could ascertain whether those genes affected virulence. The scientists then observed how laboratory mice responded to the test strains. By doing so, they pinpointed the psm-alpha gene cluster (which makes PSM-alpha protein) as playing an essential role in determining CA-MRSA virulence and, ultimately, disease severity.

To understand how PSMs contribute to virulence, Dr. Otto and colleagues next examined the role of the molecules in S. aureus evasion of human immune defenses. They observed that the psm-alpha genes generated the most resistance activity and the PSM-alpha proteins were best at destroying most immune cells that help protect against infection and disease. In all instances, the PSM-alpha molecules caused the greatest destruction of white blood cells, an effect that occurred rapidly.

What was remarkable, says Dr. Otto, is that a specific sensing mechanism likely enabled S. aureus to secrete PSMs at the ideal time when host immune cells were weakest and most vulnerable to destruction. Likewise, PSM production slowed when the bacterial survival was most jeopardized.

“We’re not saying the psm-alpha gene cluster is the only element contributing to the virulence and survival of CA-MRSA, but it is a major factor,” says Dr. Otto.

Next, he and his RML colleagues will examine whether the simple presence of the psm-alpha genes create havoc with the immune system, or whether some unknown trigger causes these genes to be expressed in a harmful way. Dr. Otto’s group also is continuing to study the molecular details of how PSMs function. Ultimately they hope to identify new candidate therapeutics for CA-MRSA by studying the roles of the different PSM genes.
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NIAID is a component of the National Institutes of Health. NIAID supports basic and applied research to prevent, diagnose and treat infectious diseases such as HIV/AIDS and other sexually transmitted infections, influenza, tuberculosis, malaria and illness from potential agents of bioterrorism. NIAID also supports research on basic immunology, transplantation and immune-related disorders, including autoimmune diseases, asthma and allergies.

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 http://www.nih.gov

PRESS RELEASE: CDC estimates 94,000 invasive drug-resistant staph infections occurred in the U.S. in 2005

Maureen Martino — Wed, 17 Oct 2007 13:29:33 -0400

CDC estimates 94,000 invasive drug-resistant staph infections occurred in the U.S. in 2005

Study establishes baseline for MRSA infection estimates
Methicillin–resistant staph aureus (MRSA) caused more than 94,000 life–threatening infections and nearly 19,000 deaths in the United States in 2005, most of them associated with health care settings, according to the most thorough study of life–threatening infections caused by these bacteria, experts with the Centers for Disease Control and Prevention (CDC) report.

The study in the Oct. 17 edition of the Journal of American Medical Association (JAMA) establishes the first national baseline by which to assess future trends in invasive MRSA infections. MRSA infections can range from mild skin infections to more severe infections of the bloodstream, lungs and at surgical sites.

The study found about 85 percent of all invasive MRSA infections were associated with health care settings, of which two–thirds surfaced in the community among people who were hospitalized, underwent a medical procedure or resided in a long–term care facility within the previous year. In contrast, about 15 percent of reported infections were considered to be community–associated, which means that the infection occurred in people without documented health care risk factors.

The 2005 rates of invasive infection were highest among people 65 years of age or older. Black people were affected at twice the rate of whites, which could be due to higher rates of chronic illness among blacks.

“These numbers show that many families are being affected by these drug–resistant infections,” said Denise Cardo, M.D., director of CDC′s Division of Healthcare Quality Promotion. “Healthcare facilities need to make MRSA prevention a greater priority. The closer we get to 100 percent compliance with CDC recommendations, the greater the impact on patient health and safety.”

Experts arrived at the new national estimate by projecting from the number of invasive MRSA cases from nine U.S. sites. The sites included the state of Connecticut; the Atlanta metropolitan area; the San Francisco Bay area; the Denver metropolitan area; the Portland, Ore., metropolitan area; Monroe County, N.Y.; Baltimore City, Md.; Davidson County, Tenn.; and Ramsey County, Minn. All the sites were part of CDC′s Active Bacterial Core surveillance program, which actively tracks a number of pathogens in the United States representing a population of 38 million Americans.

In health care settings, MRSA occurs most frequently among patients who undergo invasive medical procedures or who have weakened immune systems and are being treated in hospitals and health care facilities such as nursing homes and dialysis centers.

For more information on MRSA, please visit http://www.cdc.gov/ncidod/diseases/submenus/sub_mrsa.htm. For more information on CDC′s guidelines for the prevention of MRSA in health care settings, visit http://www.cdc.gov/ncidod/dhqp/ar_mrsa_prevention.html.

MRSA related Press Releases

PRESS RELEASE: Scientists Identify Factor Key to Severity of Community-Associated Methicillin-Resistant Staph Infections

PRESS RELEASE: CDC estimates 94,000 invasive drug-resistant staph infections occurred in the U.S. in 2005