NIH Modifies Spectinomycin To Treat Tuberculosis

The National Institute of Health (NIH) has issued a press release, announcing that researchers have found a way to use an old antibiotic to treat tuberculosis (TB). Researchers at the NIH, along with the National Institute of Allergy and Infectious Diseases (NIAID), have developed a synthetic form of spectinomycin. The new form, unlike the original drug, acts against TB. Christine Sizemore, Ph.D., Chief, Tuberculosis, Leprosy and other Mycobacterial Diseases Branch, NIAID, will act as spokesperson for this research. The study, “Spectinamides: A new class of semisynthetic anti-tuberculosis agents that overcome native drug efflux” is published in the Nature Medicine journal.

Tuberculosis

Tuberculosis is a bacterium, Mycobacterium tuberculosis. It invades the body usually in the lungs, but may infect the brain or spine, and the disease can be fatal if not treated. TB is airborne, spreading when an infected person expels the bacteria by coughing, sneezing, or speaking. People nearby breathe in the bacteria and may or may not become sick, so that some have an active TB infection or a latent one. People with latent TB are able to fight the infection and in turn do not spread the disease unless the bacteria turn active, thereby turning the person contagious. A latent infection can stay dormant for years until the immune system becomes compromised and the bacteria activate and multiply.

Spectinamides

Standard spectomycin does not work on TB because the bacteria have a pump mechanism to expel the drug. The synthesized drug overcame that mechanism. The new compound worked against drug-resistant TB, but did not harm other cells. Therefore, the medication can be taken orally, as it will not interfere with naturally occurring stomach and intestinal bacteria. Tests in mice with chronic or acute TB were also positive. Researchers have dubbed the synthetic drug “spectinomides.”

The scientists used a structure-based design to generate spectinomycin analogs. These analogs have selective ribosomal inhibition and narrow-spectrum anti-tubercular activity. In a variety of studies, the drug “significantly reduced” lung mycobacteria and improved survival rates. The structural design is thought to be the key to the analog’s efficacy, as the modifications allowed it to bypass the Rv1258c efflux pump. Study authors are optimistic that structural changes in drugs may expand drug development opportunities.

Source:

http://www.niaid.nih.gov/news/newsreleases/2014/Pages/spectinomycin.aspx