Researchers from Johns Hopkins University and Medicine have designed a potential new antibiotic for a pathogen that is highly resistant to drugs and is often lethal to individuals suffering from lung diseases, including cystic fibrosis.
Called Mycobacterium abscessus, the pathogen is associated with a commonly known bacterium that causes leprosy and tuberculosis but has lately evolved as a distinct species that often manifests as a virulent lung infection.
The researchers from the Department of Chemistry at Krieger School of Arts & Sciences and the infectious diseases department of the School of Medicine have published their results in the Communications Biology journal.
The researchers have designed one of the first promising treatments of a microbe that has a cure rate of less than 50% and no FDA-approved treatments. Before the compound, known as T405, can become a viable clinical treatment, investigators should enhance its pharmacological potency through a preclinical animal infection model.
People die of this in our hospitals every week. The data we have is very promising.”
Craig Townsend, Professor of Chemistry, Johns Hopkins University
Professor Townsend has also worked as a principal investigator on the study together with an associate professor of medicine, Gyanu Lamichhane.
In spite of years of urgent calls for additional studies to interpret the bacteria and to seek potential treatments, scientists have been cautious of testing the most harmful member of its Non-Tuberculosis Mycobacteria (NTM) family.
It’s still considered an emerging disease. There are now more NTM than tuberculosis cases in the United States. And this is the most virulent of all of them.”
Gyanu Lamichhane, Associate Professor of Medicine, Johns Hopkins University
According to the article, the T405 compound has shown a “superior potency against M. abscessus” over two widely used antibiotics. When paired with a current drug, known as avibactam, the T405 compound was also able to inhibit the bacteria from developing resistance.
Furthermore, the T405 compound was well tolerated in mice and can possibly be administered less than present-day treatments. This approach will expose patients to fewer toxic side effects, like deafness.
Individuals with lung diseases and depressed immune systems also face a risk of contracting an infection that is often seen in patients with cystic fibrosis. Transmission is yet to be fully interpreted, but the microorganisms can be detected in water, dust, and soil. It induces infections in the lungs, skin, and soft tissues.
According to the article, present therapeutic guidelines for the infection need 12 to 18 months of multidrug treatment and this has resulted in cure rates between 30% and 50%, highlighting the “need for new antibiotics with improved activity”.
Batchelder, H. R., et al. (2020) Development of a penem antibiotic against Mycobacteroides abscessus. Communications Biology. doi.org/10.1038/s42003-020-01475-2.