Dangerous MRSA Strain Evolved Recently from Common Ancestor

By Michael Smith
HAMILTON, Mont., Jan. 22 -- It may be no exaggeration to call the highly pathogenic community-acquired methicillin-resistant Staphylococcus aureus a superbug, researchers here found.
The recently identified USA300 strain, now widespread in the U.S., evolved from a single ancestor, according to Frank DeLeo, Ph.D., of the National Institute of Allergy and Infectious Diseases' Rocky Mountain Laboratories, and colleagues.
The USA300 strain of community-acquired MRSA, unknown until 2000, has become a leading cause of skin and soft-tissue disease in otherwise healthy people. But researchers had been puzzled about the origin of the USA300 strain.
Now, whole genomic sequencing shows that the USA300 isolates found across the country share a recent common ancestor, Dr. DeLeo and colleagues reported online in the Proceedings of the National Academy of Sciences.
The data rule out the competing hypothesis that various isolates derived from different ancestors had converged on the virulent USA300 strain, the researchers said.
The findings "add an evolutionary dimension to the epidemiology and emergence of USA300," Dr. DeLeo and colleagues said.
The mechanism appears to be similar to what happened in the 1950s, when a penicillin-resistant form of S. aureus (known as phage-type 80/81 S. aureus) caused a pandemic in U.S. hospitals and the community.
Currently, community-acquired MRSA is responsible for the majority of skin and soft-tissue infections in patients coming to U.S. emergency departments and the USA300 strain has been blamed for 67% of the invasive infections, the researchers noted.
Dr. DeLeo and colleagues used genetic mapping techniques to compare 10 USA300 isolates from around the U.S. with a reference strain that was sequenced in 2006.
They looked for single nucleotide polymorphisms (SNPs) -- single-letter changes in the DNA of the organism -- as well as other so-called regions of difference (RDs), such as insertions or deletions of genetic material.
The key finding was that eight of the 10 isolates were nearly identical, with an average difference from the reference strain of only 32 SNPs and from each other of just 50 SNPs, Dr. DeLeo and colleagues said.
An indication of relatively recent divergence is the ratio of non-synonymous to synonymous SNPs -- those that lead to a change in the derived polypeptide sequence versus those that make no change.
In this case, Dr. DeLeo and colleagues said, the ratio was a "relatively high" 1.9:1 and when only the eight most closely related isolates were considered, the ratio was 2.6:1.
The only reasonable interpretation "is that there has been very recent clonal expansion and geographic dissemination" of USA300, ruling out the possibility of convergent evolution, they said.
Interestingly, not all of the isolates were equally virulent in mice.
Animals infected with two of the isolates lived significantly longer (P=0.0002) than those infected with the reference strain -- even though all were genetically similar.
The inference is that even small changes in DNA can make large changes in the virulence of the organism, Dr. DeLeo and colleagues said.
"It is reasonable to conclude that within a short period there will be an increasing pool of derivative USA300 isolates that differ in virulence potential and/or pathogenicity," the researchers said.
The research was supported by NIAID.
The researchers reported no conflicts.
Primary source: Proceedings of the National Academy of SciencesSource reference:Kennedy AD, et al "Epidemic community-associated methicillin-resistant Staphylococcus aureus: recent clonal expansion and diversification" PNAS 2008; DOI: 10.1073/pnas.0710217105.