Infections from antibiotic-resistant bacteria are difficult to treat and are responsible for over 2.8 million infections and more than 35,000 deaths in the U.S. each year. A new study in Nature Communications reports that a drug used to lower blood pressure could also be the basis of a promising new treatment for methicillin-resistant Staphylococcus aureus (MRSA).
"MRSA commonly causes infections in both hospitals and the community. It infects people in different ways and can survive even when antibiotics are used, which makes treatment extremely difficult," said corresponding author Eleftherios Mylonakis, M.D., Ph.D., chair, Houston Methodist Charles W. Duncan Jr. Department of Medicine. "Scientists around the world are looking at various ways to provide treatment options outside of established antibiotics. The high cost of developing new drugs, and the time it takes to do so, led our team to explore the possibility of using existing medications, approved for other uses, to treat bacterial infections."
Researchers were interested in determining if existing drugs can change the physical properties of bacterial membranes, which can weaken the bacteria and make the bacteria more susceptible to treatment. The blood pressure drug Candesartan cilexetil (CC), a common and inexpensive medication already used clinically, was identified as having this potential.
In the lab, Dr. Nagendran Tharmalingam, first author of the study, and a team of researchers and collaborators were able to prove that the drug effectively fights MRSA by disrupting its cell membrane and interfering with cell function. It not only killed MRSA bacteria at different growth stages, but also reduced the formation of biofilms, which are clusters of the bacteria that are more difficult to treat. By weakening the bacteria and stopping its growth, researchers showed that the drug has the potential to be a tool in the arsenal of treatment options for antibiotic-resistant infections.
Other collaborators on the study included Robert Wilson-Kovacs and Orlando Acevedo from the University of Miami; Suelen Scarpa de Mello and Michael Gilmore from Harvard Medical School and Massachusetts Eye and Ear Infirmary; Philip Rupert Baldwin and Steven Ludtke from Baylor College of Medicine; Harikrishna Sekar Jayanthan from Vanderbilt University; Kulandaisamy Arulsamy from Boston Children's Hospital; Rajmohan Rajmuthiah,. Fernanda Cristina Possamai Rossatto, Katherine Manz and Kurt Pennell from Brown University; Joseph DeGiorgis from Providence College and Frederick Ausubel from Harvard Medical School and Massachusetts General Hospital.
