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 July 29, 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 July 29, 2014).

Share This




More Health & Medicine News

Tuesday, July 29, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Deadly Ebola Virus Threatens West Africa

Deadly Ebola Virus Threatens West Africa

AP (July 28, 2014) West African nations and international health organizations are working to contain the largest Ebola outbreak in history. It's one of the deadliest diseases known to man, but the CDC says it's unlikely to spread in the U.S. (July 28) Video provided by AP
Powered by NewsLook.com
$15B Deal on Vets' Health Care Reached

$15B Deal on Vets' Health Care Reached

AP (July 28, 2014) A bipartisan deal to improve veterans health care would authorize at least $15 billion in emergency spending to fix a veterans program scandalized by long patient wait times and falsified records. (July 28) Video provided by AP
Powered by NewsLook.com
Two Americans Contract Ebola in Liberia

Two Americans Contract Ebola in Liberia

Reuters - US Online Video (July 28, 2014) Two American aid workers in Liberia test positive for Ebola while working to combat the deadliest outbreak of the virus ever. Linda So reports. Video provided by Reuters
Powered by NewsLook.com
Traditional African Dishes Teach Healthy Eating

Traditional African Dishes Teach Healthy Eating

AP (July 28, 2014) Classes are being offered nationwide to encourage African Americans to learn about cooking fresh foods based on traditional African cuisine. The program is trying to combat obesity, heart disease and other ailments often linked to diet. (July 28) Video provided by AP
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:
from the past week

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