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Superbug Genetic Code Cracked, Resistance Factor Identified

MRSA bacteria (CDC)
Scanning electron micrograph image of MRSA bacteria (Janice Haney Carr, Centers for Disease Control and Prevention)

Researchers at Massachusetts Eye and Ear Infirmary in Boston, with colleagues in the U.S. and U.K., have sequenced the genomes of the 12 available strains of Staphylococcus aureus bacteria resistant to the drug vancomycin, and determined the piece of the genome that makes the strains resistant. The team published its findings yesterday in the online journal mBio.

Antimicrobial resistance is the term given to infections caused by microorganisms that fail to respond to conventional treatment, resulting in prolonged illness and greater risk of death. One type of antimicrobial resistance, methicillin resistant Staph. aureus (MRSA), is often contracted in hospital settings. From 1999 to 2005, the number of MRSA-related hospitalizations in the U.S. doubled to more than 278,000, with more than 6,600 deaths attributed to MRSA.

The last line of defense in these cases is the drug vancomycin, but the authors report that since 2002 a new type of MRSA became resistant to the drug, with this variety called VRSA. Some 11 VRSA cases have been documented since 2002, with most cases occurring in in foot and limb infections of diabetics who are often in and out of health care facilities. Each of these infections is believed to have had multiple bacteria, an MRSA plus a vancomycin resistant bacterium called Enterococcus, or VRE.

The team led by Veronica Kos and Michael Gilmore of Massachusetts Eye and Ear, with colleagues from the Broad Institute, Tufts University, University of Maryland, University of Rochester, and Wellcome Trust Sanger Institute in the U.K. have now determined the genome sequence for all available VRSA strains. The researchers identified features in the genomes that appear to make it easier for certain MRSA to acquire resistances in multiple-bacteria infections.

The researchers showed resistance arises independently in each strain after it acquires a specific bit of genetic material called transposon Tn1546. A transposon is a small mobile genetic element that moves around the genome or to other genomes within the same cell. The findings suggest the transposon likely comes from VRE bacteria that simultaneously infects the patients.

“What we found was that this group of MRSA has properties that appear to make it more social, so they can live with other bacteria like Enterococcus,” says Kos, a research associate in Gilmore’s lab and first author of the study. “This would allow those MRSA to more easily pick up new resistances.”

The Harvard-wide Antibiotic Resistance Program — Mass. Eye and Ear is affiliated with Harvard University — is using this information to develop new ways to prevent and treat infection by MRSA, VRSA, and VRE. The researchers also identified several new compounds that stop MRSA by hitting new targets, and are further testing these compounds.

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