Enzymatic Cocktail Outperforms Antibiotics Against Mycobacteria, Including TB

The growth of antibiotic resistance has put pressure on the search for new antibiotics. A recent study published in Microbiology Spectrum, a journal of the American Society for Microbiology, demonstrates that an enzymatic cocktail has the capability to eliminate various mycobacterial species of bacteria, including those responsible for tuberculosis.

Bacteria Mycobacterium tuberculosis, the causative agent of tuberculosis, 3D illustration, can be used for M. leprae, M. avium complex and other mycobacteria

Image Credit: Kateryna Kon/Shutterstock.com

This research was conducted by scientists at Colorado State University and Endolytix Technologies.

We have a mycobacterial drug that works for Nontuberculous Mycobacteria and M. tuberculosis that is biological, not phage therapy, and not small molecule antibiotics. 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.”

Jason Holder Ph.D., Study Co-Author, Founder and Chief Science Officer, Endolytix Technology

In this new proof of principle study, an enzyme cocktail that targets the mycobacteria cell envelope was created by the researchers using a biological method rather than a chemical one. The highly specific biochemical catalysts in the enzyme cocktail target and destroy the mycobacteria cell envelope, which is necessary for the survival of mycobacteria.

The enzymatic drug was administered by the researchers inside the host macrophages where the mycobacteria grow to increase its efficacy. The medication demonstrated efficacy against M. tuberculosis and Nontuberculous Mycobacteria (NTMs), two deadly pulmonary lung diseases (PD). Approximately 1.5 million people die from TB each year.

We characterized the mechanism of bactericide as through shredding of the bacterial cells into fragments. 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.”

Jason Holder Ph.D., Study Co-Author, Founder and Chief Science Officer, Endolytix Technology

The new therapy does not have many of the drug-drug interactions that are an issue with many anti-mycobacterial drugs currently in use, and it complements existing standard-of-care medications, according to study coauthor Richard Slayden, Ph.D., a Professor in the Department of Microbiology, Immunology and Pathology at Colorado State University.

Endolytix enzymes work powerfully with standard-of-care antibiotics to kill bacteria with lower drug concentrations. 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.”

Jason Holder Ph.D., Study Co-Author, Founder and Chief Science Officer, Endolytix Technology

Source:
Journal reference:

Bartlett, P., H., et al. (2024) Targeting intracellular nontuberculous mycobacteria and M. tuberculosis with a bactericidal enzymatic cocktail. Microbiology Spectrum. doi.org/10.1128/spectrum.03534-23

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