Insights into MRSA Epidemic

NIH scientists and their colleagues in China have identified a gene that’s been playing a pivotal role in epidemic waves of methicillin-resistant Staphylococcus aureus (MRSA) infections in Asia. The finding suggests a potential target for novel therapeutics.

Photo of a Chinese female doctor using a microscope in a laboratory

Decades ago, doctors used penicillin to treat people infected with the S. aureus bacterium, commonly known as staph. When S. aureus developed resistance to the antibiotic, doctors turned to methicillin. In 1961, scientists identified the first strains of S. aureus bacteria that resisted methicillin. MRSA is now a leading cause of severe infections in hospitals.

Since bacteria inherit identical copies of their mother cell's genes, lineages are referred to as clones. MRSA epidemics occur in waves, with old clones of MRSA bacteria disappearing and new clones emerging. A limited number of MRSA clones are responsible for most MRSA infections worldwide.

In China and large parts of Asia, ST239 is the predominant MRSA lineage. Recently, genome sequencing of ST239 revealed a rare new gene. A research team led by Dr. Michael Otto of NIH's National Institute of Allergy and Infectious Diseases (NIAID) and Dr. Yuan Lu of Fudan University in Shanghai set out to study whether the new gene, which they called sasX, might play a role in the spread of MRSA in China.

The researchers analyzed 807 patient samples of invasive S. aureus taken over the past decade from 3 Chinese hospitals. In the early online edition of Nature Medicine on April 22, 2012, they reported that sasX is more prevalent in MRSA strains from China than previously thought. They found that the gene's frequency is also increasing: From 2003 to 2011, the percentage of MRSA samples containing sasX almost doubled, from 21% to 39%.

Most of the sasX-positive samples in the study were from ST239. However, while sasX was found almost exclusively among ST239 strains early in the study, its frequency among other clonal types increased considerably since then, from 5% in 2003–2005 to 28% in 2009–2011. This supports a long-held theory that new clones of virulent MRSA arise through the exchange of DNA between different strains. Indeed, the sasX gene is embedded in a so-called mobile genetic element, a DNA segment that can transfer easily between strains.

The researchers next explored the biological role of sasX. They found that the protein coded by sasX appears at the S. aureus cell surface. A series of laboratory and mouse studies showed that sasX helps the bacteria to colonize the nose and cause skin abscesses and lung disease. The protein also helps the bacteria evade human immune defenses.

Taken together, these findings establish sasX as a crucial factor in MRSA's virulence and a probable driving force of the Asian MRSA epidemic. “This research helps us understand how new, more dangerous forms of MRSA can keep appearing,” Otto says.

Based on their observations, the researchers predict that sasX is likely to continue to spread. They plan to keep monitoring its progress. They're also working to develop therapeutics against MRSA strains that express sasX.