Mass. Eye and Ear receives NIAID grant to coordinate Harvard-wide Project on Antibiotic Resistance

The Massachusetts Eye and Ear Infirmary has received an $11 million grant from the National Institute of Allergy and Infectious Disease, the largest National Institutes of Health grant in this hospital's187-year history, to coordinate the Harvard-wide Project on Antibiotic Resistance.

The goal of the project, led by Dr. Michael S. Gilmore, Sir William Olser Professor of Ophthalmology, is to develop new antibiotics to treat highly resistant infections caused by staph and other related bacteria. Dr. Gilmore is a part of the Howe Laboratory of Ophthalmology at Mass. Eye and Ear.

"Infections from multidrug-resistant bacteria are leading complications of surgeries, from cataract extractions to knee replacements. Understanding how resistance develops in these strains will help guide the judicious and effective use of antibiotics, and the development of new treatments that will benefit patients and reduce health care spending," said Joan W. Miller, M.D., Henry Willard Williams Professor of Ophthalmology, Chief of Ophthalmology at Mass Eye and Ear and Mass General Hospital, and Chair of Ophthalmology at Harvard Medical School.

Since 2005, drug resistant Staphylococcus aureus has killed more people in the United States than HIV/AIDS, and it has become a leading public health concern. Because resistant staph infections are spread by hand-to-hand contact, workout facilities now provide hand sanitizers and routinely sanitize equipment. An outbreak of methicillin-resistant Staphylococcus aureus infection among the St. Louis Rams brought the problem into sharp public focus.

According to Dr. Gilmore, human beings all carry the bacterium Staphylococcus aureus somewhere on their bodies. They prefer moist areas and usually live in the nose, but also occur on the skin, in areas like armpits and groin, and elsewhere in and on the human body. Most of the time these microbes are just eking out a living and not doing any harm - they may even be protecting us from something worse. However, to hold them in check, a body needs to be in good health. Turf burns, as in the case of the St. Louis Rams football team, surgery or hospitalization, and other diseases can tip the balance in favor of the microbe. Among hospitalized patients, staphylococcal infection is the largest infectious disease problem, and its prevention is a top concern.

Dr. Gilmore recruited a team of investigators from across the Harvard University landscape, and also from industry, to tackle the problem of developing new drugs to treat these infections. Massachusetts General Hospital scientists and physicians Drs. Eleftherios Mylonakis, Fred Ausubel, and David Hooper are pursuing new strategies for discovering and testing drugs using model systems. Harvard Medical School professors Drs. Suzanne Walker and Roberto Kolter are using high-throughput robotics to identify potential drugs that target the bacterial cell surface, and its organization. Dr. Kolter and Harvard Faculty of Arts and Science professor Dr. Richard Losick are exploring new approaches for disorganizing bacterial biofilms, making the microbes easier to treat with new and existing antibiotics. Dr. Keeta Gilmore is responsible for coordinating the moving parts, and for cultivating an atmosphere that promotes synergy between projects. This group converges twice monthly at the Mass. Eye and Ear to discuss progress and to coordinate activities.

According to Dr. Gilmore, early efforts stemming originally from the Walker lab and involving most of the collaborators have already turned up one promising lead compound that is in its second generation. He hopes the five-year project will generate between five and ten promising and tested new compounds for fighting multidrug-resistant infection caused by staph and related microbes including the highly challenging vancomycin-resistant Enterococcus. A group consisting of Drs. Jared Silverman (Cubist Pharmaceuticals, Inc.), Steve Projan (MedImmune, LLC), Chris T. Walsh (HMS), and Nathanael Grey (HMS), who are highly familiar with the process of moving new drugs from the bench to bedside, will be advising the Harvard-wide collaborative team.