Key Point

Research shows that the epidemic strain of MRSA developed from a single strain of the disease, not multiple strains as has been previously suggested.

NEW ORLEANS—Researchers have discovered that the epidemic form of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infection originates from a single strain of bacteria, not multiple strains as previously believed. The research, led by Frank R. DeLeo, PhD, of the NIH’s National Institute of Allergy and Infectious Diseases at the Rocky Mountain Laboratories in Hamilton, Montana, is the first in which investigators have used comparative genome sequencing to reveal the origins of epidemic CA-MRSA. The findings were published in the January 29 Proceedings of the National Academy of Sciences.

“Our study confirms that a single strain, called USA300, of CA-MRSA is responsible for many of the devastating infections which have spread rapidly across the United States in recent years,” said James Musser, MD, PhD, coauthor of the study and Codirector of the Methodist Hospital Research Institute in Houston. The findings rule out the previously held possibility that multiple strains of USA300 emerged randomly with similar characteristics.

To clarify how CA-MRSA is evolving in complexity and spreading geographically, Dr. DeLeo’s group sequenced the genomes of 10 patient samples of the USA300 bacterium recovered from individuals treated at different US locations between 2002 and 2005. They then compared these genomes to each other and to a baseline USA300 strain used in earlier studies. Eight of the 10 USA300 patient samples were found to have nearly indistinguishable genomes, indicating they originated from a common strain. The remaining two bacteria were related to the other eight, but more distantly.

“Eight of 10 isolates analyzed had very few single nucleotide polymorphisms and thus were closely related, indicating recent diversification rather than convergence,” the researchers stated. “Unexpectedly, two of the clonal isolates had significantly reduced mortality in a mouse sepsis model compared with the reference isolate,” which shows that minimal genetic change in the bacterial genome can profoundly affect disease severity and risk of drug resistance, they added.

“Taken together, our results demonstrate that there has been recent clonal expansion and diversification of a subset of isolates classified as USA300,” Dr. DeLeo and colleagues pointed out. “The findings add an evolutionary dimension to the epidemiology and emergence of USA300 and suggest a similar mechanism for the pandemic occurrence and spread of penicillin-resistant S aureus (known as phage-type 80/81 S aureus) in the 1950s.” The investigators noted that although strains of phage-type 80/81 died out with the introduction of methicillin in 1959, the emergence of MRSA currently epidemic in hospitals occurred nearly immediately afterward.

“The USA300 group of strains appears to have extraordinary transmissibility and fitness,” said Dr. 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.” Ultimately, Dr. DeLeo and his colleagues hope that their work will lead to the development of new diagnostic tests that can quickly identify specific strains of MRSA, as well as treat the disease.           

Suggested Reading
John JF Jr, Lindsay JA. Clones and drones: do variants of Panton-Valentine leukocidin extend the reach of community-associated methicillin-resistant Staphylococcus aureus? J Infect Dis. 2008;197(2):175-178.
Kennedy AD, Otto M, Braughton KR, et al. Epidemic community-associated methicillin-resistant Staphylococcus aureus: recent clonal expansion and diversification. Proc Natl Acad Sci U S A. 2008;105(4):1327-1332.
Monecke S, Slickers P, Ellington MJ, et al. High diversity of Panton-Valentine leukocidin-positive, methicillin-susceptible isolates of Staphylococcus aureus and implications for the evolution of community-associated methicillin-resistant S aureus. Clin Microbiol Infect. 2007;13(12):1157-1164.
O’Hara FP, Guex N, Word JM, et al. A geographic variant of the Staphylococcus aureus Panton-Valentine leukocidin toxin and the origin of community-associated methicillin-resistant S aureus USA300. J Infect Dis. 2008;197(2):187-194.

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