Public Release:  Harvard team cracks code for new drug resistant superbugs

Massachusetts Eye and Ear Infirmary

Summary: National Institutes of Health-funded scientists have determined the genetic sequences of all 12 available strains of Staphylococcus aureus bacteria resistant to vancomycin--an antibiotic of last resort--and have demonstrated that resistance arose independently in each strain after it acquired a specific bit of genetic material called transposon Tn1546. The transposon likely came from vancomycin-resistant Enterococcus bacteria that simultaneously infected the patients. The team also identified shared features among the vancomycin-resistant staph strains that may have helped them acquire Tn1546 and evade human immune defenses. Their findings are reported in the May 22 issue of the journal mBio®.

Boston (May 22, 2012) - Antibiotic-resistant superbugs, including methicillin resistant Staph. aureus (MRSA), have become household words. Antibiotic resistance threatens health and lives. Schools have been closed, athletic facilities have been scrubbed, and assisted living and day care centers have been examined for transmission of these bacteria. Since 2005, MRSA have killed over 18,000 people a year in the United States alone.

To make matters worse, in 2002 a new MRSA with resistance to even the last-line drug vancomycin (VRSA) appeared. Since the first case in Michigan, there have been at least 11 other well-documented cases in New York, Pennsylvania, Delaware and more in Michigan. Scientists at the Centers for Disease Control, Harvard University and elsewhere have been working to determine the origin of these VRSA, to understand why they have turned up, and to understand the risk of spread. Most VRSA occurred 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). VRE has caused vancomycin resistant hospital-acquired infections since the 1980s.

But there is hope on the horizon. Scientists have now determined the genome sequence for all available VRSA strains. The Harvard-wide Antibiotic Resistance Program is using this information to develop new ways to prevent and treat infection by MRSA, VRSA and VRE. The team identified several new compounds that stop MRSA by hitting new targets, and is currently subjecting these to further tests. This group works closely with partners at the Broad Institute and Harvard's Microbial Sciences Initiative.

To sequence the genomes, researchers from the National Institutes of Health (NIH)-funded Harvard-wide Antibiotic Resistance Program, headquartered at the Massachusetts Eye and Ear in Boston, assembled an elite international team. Headed by Harvard professor Michael Gilmore, Ph.D., and his associate Veronica Kos, Ph.D., both based at Mass. Eye and Ear, the team included bioinformatics and genomics experts from the Broad Institute of MIT and Harvard, the Institute for Genome Sciences of the University of Maryland, the University of Rochester, and the Wellcome Trust Sanger Center in the UK. They identified features in the genomes that appear to have made it easier for certain MRSA to acquire resistances in mixed infection. Their findings are reported in the May 22 issue of the journal mBio®, the American Society of Microbiology's first broad-scope, online-only, open access journal.

"The genome sequence gave us unprecedented insight into what makes these highly resistant bacteria tick. Several things were remarkable," says Gilmore. "Vancomycin resistance repeatedly went into just one tribe of MRSA, so the question became 'what makes that group special -- why did they start getting vancomycin resistance?"'

"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. This would allow those MRSA to more easily pick up new resistances," adds Kos. "The good news is that some of these properties weaken the strain's ability to colonize, and may be limiting their spread."

Gilmore is the Sir William Osler Professor of Ophthalmology, and also serves in the Department of Microbiology and Immunobiology at Harvard Medical School. Kos is a senior research associate in the Gilmore lab. They and colleagues from Harvard's Microbial Sciences Initiative formed the NIH sponsored Harvard-wide Antibiotic Resistance Program in 2009.

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Authors: Veronica N. Kos, Christopher A. Desjardins, Allison Griggs, Gustavo Cerquiera, Andries Van Tonder, Matthew T.G. Holden, Paul Godfrey, Kelli L. Palmer, Kip Bodi, Emmanuel F. Mongodin, Jennifer Wortman, Michael Felgarden, Trevor Lawley, Steven R. Gill, Brian J. Hass, Bruce Birren and Michael S. Gilmore (list of affiliations available in the PDF)

Grant Support: This research was supported in part with Federal funds from the National Institute of Allergy and Infectious Disease (NIAID) including the Harvard-wide Program on Antibiotic Resistance (NIH grant AI083214), Contract No.: HHSN27220090018C to the Broad Institute, Contract HHSN272200700055C for the Network on Antimicrobial Resistance in Staphylococcus aureus Program (NARSA), and National Eye Institute (NEI) grant EY017381 (MSG). Both the NIAID and NEI are parts of the National Institutes of Health.

About Mass. Eye and Ear

The Mass. Eye and Ear/Mass General Department of Ophthalmology is one of the world's premier centers for excellence in ophthalmic clinical care, research and education. Steadfast dedication to an integrated three-part mission keeps the Department at the forefront of advances in patient care and scientific discovery, while training and advancing generations of leaders through our academic and professional development programs. As the seat of Ophthalmology leadership for Harvard Medical School, the Department builds on the strengths of faculty from such renowned local institutions as Joslin Diabetes Center, Children's Hospital Boston, the Mass. Eye and Ear-affiliated Schepens Eye Research Institute, Brigham and Women's Hospital, Beth Israel Deaconess Medical Center and Boston Veteran's Administration Healthcare System to encourage innovation and remain a global leader in ophthalmology.

Founded in 1824, Mass. Eye and Ear is an independent specialty hospital, an international center for treatment and research, and a teaching affiliate of the Harvard Medical School.

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