Featured Research

from universities, journals, and other organizations

New Class Of Tuberculosis-Fighting Antibiotics Suggested By Biochemical-Pathway Study

Date:
April 7, 2005
Source:
University Of Pennsylvania Medical Center
Summary:
A worldwide health problem, tuberculosis kills more people than any other bacterial infection. The World Health Organization estimates that two billion people are infected with TB, and that two million people die each year from the disease.

Philadelphia, PA - A worldwide health problem, tuberculosis kills more people than any other bacterial infection. The World Health Organization estimates that two billion people are infected with TB, and that two million people die each year from the disease.

However, due to multi-drug resistance and a protracted medication regimen, it is extremely difficult to treat. Hence, there is still a great deal of interest in developing new anti-tubercular drugs. Researchers at the University of Pennsylvania School of Medicine have identified a biochemical target that could lead to a new class of antibiotics to fight TB. They report their findings in this week’s online edition of the Proceedings of the National Academy of Sciences .

In a proof-of-principle study, Harvey Rubin, MD, PhD, Professor of Medicine, Division of Infectious Diseases, and colleagues were able to stop the bacteria from multiplying by inhibiting the first step in a common biochemical pathway. This pathway is responsible for making the energy molecules all cells need to survive. First author Edward Weinstein, an MD/PhD student, Rubin, and colleagues characterized the pathway and showed that an important enzyme in it is a key target for anti-TB agents.

The pathway, explains Rubin, is like a series of links in a chain, with enzymes facilitating reactions along the way. “We discovered that if you inhibit the very first enzyme in the chain, you inhibit everything else downstream and eventually the bacteria die,” he explains.

The research group tested phenothiazine, a drug used in the past to treat schizophrenia, in cultures of Mycobacterium tuberculosis, the bacterium that causes TB. They found that phenothiazines killed the bacterium in culture and suppressed its growth in mice with acute TB infection.

While the effect on the growth of TB in mice was small, it suggested that a valid target was identified. The research group went on to show that the enzyme disabled by the phenothiazines is called type II NADH dehydrogenase and is a unique and important antimicrobial target.

“What we have now is a new target in TB,” says Rubin. “We’ve been able to find at least the beginnings of a class of compounds that we can start working with and that we know is biochemically active against the TB bacteria in culture and in small animals.”

Is it a new drug for tuberculosis? Not yet, cautions Rubin. It’s premature to say that this class of drugs will cure TB, but it does represent the start of basic research towards that, he concludes. Next steps include more investigations on inhibitors of the NADH biochemical pathway in TB, and the development of high-throughput screens to find better and safer inhibitors of type II NADH dehydrogenase.

This work was supported by grants from the National Institutes of Health. Rubin and Weinstein’s coauthors are Takahiro Yano, Lin-Sheng Li, David Avarbock, Andrew Avarbock and Douglas Helm from Penn, and Andrew McColm, Ken Duncan, and John T. Lonsdale from GlaxoSmithKline (Collegeville, PA and Stevenage, UK). Animal studies were conducted at GlaxoSmithKline. Penn researchers report no conflicts of interest.


Story Source:

The above story is based on materials provided by University Of Pennsylvania Medical Center. Note: Materials may be edited for content and length.


Cite This Page:

University Of Pennsylvania Medical Center. "New Class Of Tuberculosis-Fighting Antibiotics Suggested By Biochemical-Pathway Study." ScienceDaily. ScienceDaily, 7 April 2005. <www.sciencedaily.com/releases/2005/03/050329131351.htm>.
University Of Pennsylvania Medical Center. (2005, April 7). New Class Of Tuberculosis-Fighting Antibiotics Suggested By Biochemical-Pathway Study. ScienceDaily. Retrieved October 20, 2014 from www.sciencedaily.com/releases/2005/03/050329131351.htm
University Of Pennsylvania Medical Center. "New Class Of Tuberculosis-Fighting Antibiotics Suggested By Biochemical-Pathway Study." ScienceDaily. www.sciencedaily.com/releases/2005/03/050329131351.htm (accessed October 20, 2014).

Share This



More Health & Medicine News

Monday, October 20, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

How Nigeria Beat Its Ebola Outbreak

How Nigeria Beat Its Ebola Outbreak

Newsy (Oct. 20, 2014) The World Health Organization has declared Nigeria free of Ebola. Health experts credit a bit of luck and the government's initial response. Video provided by Newsy
Powered by NewsLook.com
Another Study Suggests Viagra Is Good For The Heart

Another Study Suggests Viagra Is Good For The Heart

Newsy (Oct. 20, 2014) An ingredient in erectile-dysfunction medications such as Viagra could improve heart function. Perhaps not surprising, given Viagra's history. Video provided by Newsy
Powered by NewsLook.com
Ebola Worries End for Dozens on U.S. Watch Lists

Ebola Worries End for Dozens on U.S. Watch Lists

Reuters - US Online Video (Oct. 20, 2014) Forty-three people who had contact with Thomas Eric Duncan, the first person diagnosed with Ebola in the U.S., were cleared overnight of twice-daily monitoring after 21 days of showing no symptoms. Rough Cut (no reporter narration). Video provided by Reuters
Powered by NewsLook.com
Beijing Marathon Runners Brave Hazardous Air Pollution

Beijing Marathon Runners Brave Hazardous Air Pollution

AFP (Oct. 19, 2014) Tens of thousands of runners battled thick smog at the Beijing Marathon on Sunday, with some donning masks as the levels of PM2.5 small pollutant particles soared to 16 times the maximum recommended level. Duration: 00:54 Video provided by AFP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins