Researchers Develop New Class of Antibiotics to Fight Leading Superbugs

Mass. Eye and Ear researchers have helped identify a new kind of antibiotic that can kill drug-resistant bacteria, like the Enterococcus shown above.

Boston, Mass. — In a significant advance against drug-resistant superbugs, investigators supported by the Harvard-wide Program on Antibiotic Resistance, a project administered by Massachusetts Eye and Ear, have identified a new class of synthetic antibiotics that have been shown to be effective against Staphylococcus aureus and Enterococcus. These two pathogens are among the most virulent, multi-drug resistant pathogens and are responsible for thousands of deaths each year. In a paper published online in Nature, the multidisciplinary group of researchers describe pioneering work that discovered new antibiotics that could one day help treat deadly infections caused by these superbugs.

“Antibiotic resistance is a leading public health concern that threatens everyone, especially patients who undergo complex surgeries,” said Michael Gilmore, Ph.D., the Sir William Osler Professor of Ophthalmology, and founder and director of the Harvard-wide consortium that includes collaborators from Mass. Eye and Ear, Harvard Medical School, Mass General Hospital, and Brown University. “Our consortium was created to draw leading clinician scientists and researchers from across the greater Harvard landscape to identify new antibiotics and slow the spread of resistance.” Since 2011, the National Institutes of Health has awarded Mass. Eye and Ear more than $20 million to lead the Harvard-wide program.

The successful collaboration took advantage of a new screening technology, pioneered by Harvard-wide Program scientist Frederick Ausubel, Ph.D., Professor of Genetics at Harvard Medical School and Mass General Hospital and associates. This technology uses laboratory roundworms to screen potential antibiotics to identify those that would likely be safe for animal and human use. Eleftherios Mylonakis, M.D., Ph.D., the Charles C.J. Carpenter Professor of Infectious Disease at Alpert School of Brown University, led the team of researchers in a search for novel compounds that can safely distinguish and rupture bacterial membranes, while sparing human cells.

Dr. Wooseong Kim of the Mylonakis lab, and collaborators, screened more than 82,000 compounds and identified two synthetic retinoids that were able to kill MRSA (methicillin-resistant Staphylococcus aureus), a type of staph bacteria that is highly resistant to several antibiotics. Dr. Daria Van Tyne of the Gilmore laboratory helped identify the genes responsible for making the bacterial membrane target of these drugs. Sophisticated computer modeling led by Huajian Gao, Ph.D., the Walter H. Annenberg professor of Engineering at Brown University, as well as additional studies by Dr. Kim and colleagues showed that the compounds were able to weaken the cell membranes of bacteria, and were especially effective when paired with the existing antibiotic, gentamicin. A team of chemists from Emory University modified the retinoids to retain maximum potency against MSRA, while minimizing human toxicity. 

These retinoid compounds are among the first to be highly effective at killing the most stubborn form of staph found in biofilms – communities of bacteria that can attach and grow on various surfaces such as implanted plastic and metal devices used in surgery. Biofilm-associated organisms are highly resistant to conventional antibiotics and can cause infections in patients with an artificial joint or other prosthesis – and they have the ability to form biofilms on living tissue, including the heart, lung, eye, and middle ear.

“Antibiotic-resistant bacteria are emerging faster than new antibiotics are being discovered, and organisms that infect humans have adapted to existing antimicrobials that are in widespread use ,” said Joan W. Miller, M.D., the David Glendenning Cogan Professor and Chair of Ophthalmology at Harvard Medical School, and Chief of Ophthalmology at Mass. Eye and Ear and Mass General Hospital. “This study is a great example of the power of multidisciplinary, collaborative teams, working to solve a complex problem and accelerating the development of life-saving treatments.”

About Massachusetts Eye and Ear 

Massachusetts Eye and Ear, founded in 1824, is an international center for treatment and research and a teaching hospital of Harvard Medical School. Specializing in ophthalmology (eye care) and otolaryngology-head and neck surgery (ear, nose and throat care), Mass. Eye and Ear clinicians provide care ranging from the routine to the very complex. Also home to the world's largest community of hearing and vision researchers, Mass. Eye and Ear has pioneered new treatments for blindness, deafness and diseases of the head and neck. Our scientists are driven by a mission to discover the basic biology underlying these conditions and to develop new treatments and cures. In the 2017-2018 "Best Hospitals Survey," U.S. News & World Report ranked Mass. Eye and Ear #1 in New England for eye (#4 in nation) and ear, nose and throat care (#2 in nation).For more information about life-changing care and research at Mass. Eye and Ear, please visit our blog, Focus, and follow us on Twitter and Facebook.

About Harvard Medical School Department of Ophthalmology

The Harvard Medical School (HMS) Department of Ophthalmology (eye.hms.harvard.edu) is one of the leading and largest academic departments of ophthalmology in the nation. More than 350 full-time faculty and trainees work at nine HMS affiliate institutions, including Massachusetts Eye and Ear, Schepens Eye Research Institute of Massachusetts Eye and Ear, Massachusetts General Hospital, Brigham and Women’s Hospital, Boston Children’s Hospital, Beth Israel Deaconess Medical Center, Joslin Diabetes Center/Beetham Eye Institute, Veterans Affairs Boston Healthcare System, VA Maine Healthcare System, and Cambridge Health Alliance. Formally established in 1871, the department has been built upon a strong and rich foundation in medical education, research, and clinical care. Through the years, faculty and alumni have profoundly influenced ophthalmic science, medicine, and literature—helping to transform the field of ophthalmology from a branch of surgery into an independent medical specialty at the forefront of science.