January 28, 2008

Studies Suggest How Drug-Resistant Staph Evolved

Scanning electron micrograph shows clusters of spherical staph bacteria Clusters of methicillin-resistant Staphylococcus aureus (MRSA) bacteria. Annie Cavanagh, Wellcome Images.

By studying the genomes of drug-resistant Staphylococcus aureus, scientists have found that a single, highly transmissible strain may be responsible for most community outbreaks nationwide. Just a few tiny genetic changes seem to affect disease severity and drug resistance, allowing the bacteria to become a leading cause of disease in otherwise healthy people.

Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) is a growing public health problem. CA-MRSA often spreads from one person to another through close skin-to-skin contact. The bacteria typically cause readily treatable skin infections that may look like pimples or boils. In rare cases, CA-MRSA can cause more serious, life-threatening conditions that are difficult to treat.

Only a decade ago, drug-resistant forms of the bacteria were rarely found outside of hospital settings. But MRSA has evolved to become more common in communities. In 2 studies headed by Dr. Frank DeLeo, a scientist in the Rocky Mountain Laboratories of NIH's National Institute of Allergy and Infectious Diseases (NIAID), researchers examined the evasive tactics, genetics and virulence of CA-MRSA.

In the January 2008 issue of the Journal of Immunology, the scientists showed how different strains of CA-MRSA evade white blood cells known as neutrophils, which ingest and destroy microbes. When neutrophils release their killing chemicals on CA-MRSA, the bacteria sense the attack and activate several resistance mechanisms. Some mechanisms help CA-MRSA evade the chemicals, while others directly kill the attacking neutrophils. These findings allowed the scientists to form the most complete picture to date of the bacteria's survival strategy.

In a second study, published in the early online edition of the Proceedings of the National Academy of Sciences on January 23, 2008, the researchers focused on a group of CA-MRSA strains known as USA300. USA300 has caused several community outbreaks of MRSA skin infections since it was first recognized in 2000.

The scientists analyzed and compared the entire genomes of USA300 bacteria collected from 10 patients living in diverse regions of the United States. Eight of the samples had nearly indistinguishable genomes, indicating that they originated from a common strain. The remaining 2 bacterial genomes were related to the other 8, but more distantly.

After exposing mice to the different strains, the researchers found that 2 of the 8 nearly indistinguishable samples caused far fewer deaths in laboratory mice than the others. This finding suggests that even minor genetic changes can profoundly affect bacterial virulence and the potential for developing drug resistance, the scientists say.

"The USA300 group of strains appears to have extraordinary transmissibility and fitness," says DeLeo. "We anticipate that new USA300 derivatives will emerge within the next several years and that these strains will have a wide range of disease-causing potential." He and his colleagues hope that their findings will ultimately lead to new diagnostic tests that can quickly identify specific strains of MRSA.

Related Links