New enzymatic cocktail can kill TB-causing mycobacteria
Washington, D.C., March 27, 2024 — With resistance to chemical antibiotics on the rise, the world needs entirely new forms of antimicrobials. A new study published in Microbiology Spectrum, a journal of the American Society for Microbiology, shows that an enzymatic cocktail can kill a variety of mycobacterial species of bacteria, including those that cause tuberculosis. The research was carried out by scientists at Colorado State University and Endolytix Technologies.
“We have a mycobacterial drug that works for nontuberculous mycobacteria (NTM) and M. tuberculosis that is biological, not phage therapy and not small molecule antibiotics,” said Jason Holder, Ph.D., a study coauthor and founder and Chief Science Officer of Endolytix Technology. “Mycobacterial infections are particularly hard to treat due to poor efficacy with standard-of-care drugs that are used in multidrug regimens, resulting in significant toxicities and treatments lasting 6 months to years. This is often followed up by reemergence of the bacterial infection after a year of testing negative.”
In the new proof of principle study, the researchers took a
biological approach instead of a chemical one to develop a
cocktail of enzymes that attack the cell envelope of
mycobacteria. The cocktail of enzymes contains highly specific
biochemical catalysts that target and degrade the mycobacterial
cell envelope that is essential for mycobacterial viability. To
increase efficacy, the researchers delivered the enzymatic drug
inside of host macrophages where mycobacteria grow. In
laboratory experiments, the drug was effective against
M. tuberculosis and NTMs, both lethal pulmonary lung
diseases (PD). TB kills
roughly 1.5 million people per year.
“We characterized the mechanism of bactericide as through
shredding of the bacterial cells into fragments,” Holder
said. “We’ve shown we can design and develop
biological antibiotics and deliver them to the sites of
infection through liposomal encapsulation. By combining drug
delivery science with enzymes that lyse bacteria, we hope to
open up treatment options in diseases such as NTM pulmonary
disease, tuberculosis pulmonary disease and others.”
According to study coauthor Richard Slayden, Ph.D., a
professor in the Department of Microbiology, Immunology and
Pathology at Colorado State University, the new therapy
complements current standard-of-care drugs and does not have
many of the drug-drug interactions that are problematic with
many anti-mycobacterial drugs in use. “Endolytix enzymes
work powerfully with standard-of-care antibiotics to kill
bacteria with lower drug concentrations,” Holder said.
“This has the potential to reduce the significant
toxicities associated with multi-drug regimens that are the
standard for mycobacterial infections and hopefully lead to more
rapid cures.”
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The American Society for Microbiology is one of the largest
professional societies dedicated to the life sciences and is
composed of 36,000 scientists and health practitioners. ASM's
mission is to promote and advance the microbial sciences.
ASM advances the microbial sciences through
conferences, publications, certifications, educational
opportunities and advocacy efforts. It enhances laboratory
capacity around the globe through training and resources. It
provides a network for scientists in academia, industry and
clinical settings. Additionally, ASM promotes a deeper
understanding of the microbial sciences to diverse audiences.
