MRSA bacterial strain mutates quickly as it spreads

Antibiotic-resistant microbe's detailed family tree reveals roots of the global infection

An antibiotic-resistant strain of staph bacteria began its globetrotting adventures in Europe and can mutate quickly as it spreads, a new study suggests. Scientists acting as molecular historians used a new technology to decode the bacteria’s genome and follow its movements, an approach that could one day help health care workers pinpoint the origins of outbreaks and prevent further infections.

The marauding bacterium, known as methicillin-resistant Staphylococcus aureus or MRSA, changes its genetic makeup faster than previously thought by altering at least one letter in its genetic handbook about every six weeks, a new study in the Jan. 22 Science shows.

More of those mutations fall in genes involved in antibiotic resistance than would be expected if the changes had occurred randomly, “illustrating that there is an immense selective pressure from antibiotic use worldwide,” says Simon Harris, a bacterial phylogeneticist at the Wellcome Trust Sanger Institute in Hinxton, England. Bacteria that get mutations creating resistance to antibiotics are more likely to survive than are bacteria that remain sensitive to drugs.

Harris and his colleagues report analyses of 63 isolates of a strain of MRSA, all collected in hospitals around the world. The researchers decoded the entire genetic instruction book, or genome, of each sample. All the isolates are variations of a MRSA strain known as sequence type 239, or ST239. Most of the samples look genetically identical when analyzed using other DNA fingerprinting techniques. Only after determining every letter of the genetic handbook of each sample could the researchers see that each isolate is genetically distinct, Harris says.

Recently developed DNA-decoding technology known as high-throughput sequencing drastically reduces the time and cost of deciphering a genome. The first bacterial genome in 1995, for instance, took three years and millions of dollars to decode. Now researchers can dissect up to 96 bacterial genomes in a matter of weeks.

Other microbiologists say this type of whole-genome analysis could provide a more complete picture of how infections spread. “I’m pretty excited about this,” says Frank DeLeo, a microbiologist at the Rocky Mountain Laboratories in Hamilton, Mont., of the National Institute of Allergy and Infectious Diseases. “The approach is great. It’s the direction the entire field should be moving in the future.”

Subtle genetic differences among isolates allowed researchers to construct a sort of family tree for the strain. The analysis reveals that the ST239 strain likely arose in Europe in the 1960s and has since spread to become the dominant MRSA strain in Asia. The strain remains prominent in Europe and is also common in South America. The South American samples were closely related genetically, probably indicating that a single variant invaded the continent recently and spread throughout the continent. The researchers also saw patterns indicating that intercontinental travel of the strain is a relatively rare event.

Study of 20 isolates collected in a hospital in Thailand over a five-month period showed that most of those infections originated outside of the hospital from bacteria brought in by patients, health care workers or visitors, rather than being passed from patient to patient inside the hospital. But the researchers also found evidence of a spread among five patients in adjacent hospital wards over a two-week period.

In the future, whole genome analysis might help hospitals find where outbreaks originate and devise strategies to stop the spread, says Sharon Peacock, a microbiologist at the University of Cambridge in England.

The new approach probably won’t change treatment for individual patients, DeLeo says, but it will give a more complete picture of the mutations that lead to an epidemic. “To understand how a successful pathogen emerges is critical,” he says. Armed with that information, researchers “can develop means to control similar pathogens in the future.”

Tina Hesman Saey is the senior staff writer and reports on molecular biology. She has a Ph.D. in molecular genetics from Washington University in St. Louis and a master’s degree in science journalism from Boston University.

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