Treatment for S. aureus skin infection works in mouse model

Aug 31, 2010
The USA300 strain of Staphylococcus aureus bacteria, colorized in gold, shown outside a white blood cell. Credit: RML/NIAID

Scientists from the National Institutes of Health and University of Chicago have found a promising treatment method that in laboratory mice reduces the severity of skin and soft-tissue damage caused by USA300, the leading cause of community-associated Staphylococcus aureus infections in the United States.

By neutralizing a key toxin associated with the bacteria, they found they could greatly reduce the damaging effects of the infection on and soft tissue. Community strains of S. aureus cause infection in otherwise healthy people and are considered extremely virulent, as opposed to hospital strains that infect people who already are weakened by illness or surgery.

While much recent attention has been focused on deaths caused by S. aureus infection in the bloodstream—and those caused by methicillin-resistant S. aureus in particular—the estimates that in 2005, physicians treated 14 million non-lethal S. aureus skin and soft-tissue cases in the United States.

In their study, now online in The Journal of , scientists from NIH's National Institute of Allergy and Infectious Diseases (NIAID) examined the effects of the alpha-hemolysin, or Hla, on S. aureus skin infections in laboratory mice. In all aspects of the study where the Hla toxin was either removed from S. aureus bacteria or neutralized through immunization, skin abscesses were significantly smaller, mice recovered faster and there was little or no skin destruction.

When S. aureus secretes Hla during infection in humans, the toxin pokes holes in a variety of different host cells, killing them. Scientists who have studied Hla for years have mainly focused on neutralizing the toxin in cases of pneumonia-related S. aureus infection. Until now, no one had tested how the absence of Hla would affect the severity of USA300 skin infections and whether immunization against the toxin could neutralize Hla and its contribution to the severity of skin disease.

"For cases of skin and soft-tissue infection caused by Staph aureus, this study highlights the potential for antitoxin treatment to become an effective alternative to traditional antibiotics, which we know have limitations because of drug resistance," says NIAID Director Anthony S. Fauci, M.D. Antitoxins prevent harm caused by a specific part of a pathogen—such as Hla in S. aureus—rather than trying to kill the entire pathogen, as antibiotics do.

The study, led by Frank DeLeo, Ph.D., of NIAID's Rocky Mountain Laboratories in Hamilton, Mont., documented physical differences in mice infected with different strains of S. aureus, including USA300 with or without Hla. The second portion of the study tested what is known as active and passive immunity, with mice being immunized with a non-lethal version of the toxin or injected with Hla-specific antibodies, respectively. Both types of immunization protected mice from skin lesions that typically destroy skin and surrounding tissue.

The group noted that multiple S. aureus molecules must contribute to because simply removing or neutralizing Hla did not completely prevent the formation of skin abscesses, although the abscesses were smaller in size.

Study collaborators from the University of Chicago, Olaf Schneewind, M.D., Ph.D., and Juliane Bubeck Wardenburg, M.D., Ph.D.,contributed the Hla treatment concept, which they developed through their recent work on S. aureus pneumonia. Dr. DeLeo's group adapted that work to their mouse model of skin infection, which is a good indicator of how abscess size and skin destruction could affect humans, according to the study investigators.

"This is probably one of the most promising targets we currently have in our efforts to develop therapeutics that protect against severe Staph aureus skin infections," says Dr. DeLeo. His group is continuing its collaboration with Drs. Schneewind and Bubeck Wardenburg on the project.

Explore further: Migraine may double risk for facial paralysis

Provided by National Institutes of Health

4.5 /5 (2 votes)
add to favorites email to friend print save as pdf

Related Stories

Researchers find link to severe Staph infections

Dec 23, 2008

Researchers at The University of Texas School of Public Health recently described studies that support the link between the severity of community-acquired antibiotic-resistant Staphylococcus aureus (CA MRSA) infections and th ...

Scientists Find a New Toxin That May be Key to MRSA Severity

Jul 17, 2010

A research project to identify all the surface proteins of USA300—the most common community-associated strain of the methicillin-resistant form of the bacterium Staphylococcus aureus (MRSA)—has resulted in the identification ...

Studies pinpoint key targets for MRSA vaccine

Aug 16, 2010

Two recent studies provide evidence for a new approach to vaccines to prevent infections caused by drug-resistant Staphylococcus aureus -- better known as MRSA - the leading cause of skin and soft tissue, bloodstream and lu ...

Recommended for you

Migraine may double risk for facial paralysis

26 minutes ago

Migraine headache may double the risk of a nervous system condition that causes facial paralysis, called Bell's palsy, according to a new study published in the December 17, 2014, online issue of Neurology, the medical journa ...

Anti-diabetic drug springs new hope for tuberculosis patients

7 hours ago

A more effective treatment for tuberculosis (TB) could soon be available as scientists have discovered that Metformin (MET), a drug for treating diabetes, can also be used to boost the efficacy of TB medication without inducing ...

Chikungunya virus shuts down infected cells

8 hours ago

Researchers from Wageningen University, part of Wageningen UR, in collaboration with colleagues from Leiden University and a research team in Australia, have revealed how chikungunya virus blocks essential ...

User comments : 0

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.