Using high resolution genome sequencing, an international team of researchers has tracked a particularly virulent strain of MRSA as it traveled between South America, Europe and Southeast Asia. The findings shed light on how these deadly bacteria are able to spread from patient to patient in a single hospital and, on a larger scale of geography and time, between countries and entire continents. The results appear in a recent issue of Science.

"MRSA is responsible for over 18,000 fatalities in the United States each year according to CDC estimates, a number virtually identical to the current fatality rate of AIDS in the USA," says Alexander Tomasz, who is Dr. Plutarch Papamarkou Professor and head of the Laboratory of Microbiology and Infectious Disease at Rockefeller.

Earlier studies demonstrated that the most successful MRSA strains belong to a limited number of families, or clones, that are responsible for the overwhelming majority — more than 80 percent — of all MRSA disease in hospitals worldwide.

In the new research, the scientists focused on one of the most successful MRSA clones, called the Brazilian MRSA, which was first identified at Rockefeller in 1995 and which has the DNA sequence type assignment ST239 (SCCmec III). Isolates of Brazilian MRSA are resistant to virtually all currently available antibacterial agents except vancomycin.

The researchers say the findings provide an unparalleled view of the evolutionary history and age of the Brazilian MRSA clone. It was possible to show that the most likely birthplace of Brazilian MRSA was actually Europe, from where it spread to South America and Asia. From there, it continued to evolve and was reintroduced to Europe at a later date.

Analyzing 20 Brazilian MRSA samples recovered from individual patients in a single Thai hospital within the short timeframe of a few weeks, the scientists were able to trace with precision the patient-to-patient spread of the MRSA bacterium.

"The remarkable insights that this study provides into the stages of evolution of a major human pathogen illustrates the power of collaboration between evolutionary biologists, experts in DNA sequencing and bioinformatics and epidemiologists who can provide carefully selected and characterized strain collections for each study," says Tomasz.

"The application of full genome sequencing described in the Science report provides us with a view of how MRSA evolves on two different scales of time and geography," says de Lencastre. "It not only documents evolution on the timescales of decades and over the geography of entire continents, but also on the shorter timescale of a few weeks within the confines of a single hospital in Thailand."

"It would be interesting to add to these two stories a third one in which we applied full DNA sequencing on an even shorter scale of time and space," says Tomasz. "In a recent study published in PNAS in 2007 we were able to track the in vivo evolution of multidrug resistance in a single MRSA lineage recovered from a patient undergoing a three-month course of chemotherapy."





Citation: Simon R. Harris et al., 'Evolution of MRSA During Hospital Transmission and Intercontinental Spread', Science, January 2010, 327 (5964), 469-474; doi: 10.1126/science.1182395