Featured Research

from universities, journals, and other organizations

Clues uncovered about how most important tuberculosis drug attacks its target

Date:
August 13, 2014
Source:
Johns Hopkins University Bloomberg School of Public Health
Summary:
A new clue to understanding how the most important medication for tuberculosis (TB) works to attack dormant TB bacteria in order to shorten treatment has been found by researchers. The antibiotic Pyrazinamide (PZA) has been used to treat TB since the 1950s, but its mechanisms are the least understood of all TB drugs. The PZA findings may help researchers identify new and more effective drugs not only for TB -- which can require six months or more of treatment -- but other persistent bacterial infections.

Researchers at the Johns Hopkins Bloomberg School of Public Health say they have discovered a new clue to understanding how the most important medication for tuberculosis (TB) works to attack dormant TB bacteria in order to shorten treatment.

Related Articles


The antibiotic Pyrazinamide (PZA) has been used to treat TB since the 1950s, but its mechanisms are the least understood of all TB drugs. The PZA findings may help researchers identify new and more effective drugs not only for TB -- which can require six months or more of treatment -- but other persistent bacterial infections. A report on the research is published online Aug. 13 in the journal Emerging Microbes & Infections.

"PZA is probably the most unique antibiotic we have because instead of only going after TB cells that are actively replicating, it seeks out and destroys dormant TB cells that can't be controlled by other antibiotics," says study leader Ying Zhang, MD, PhD, a professor in the Bloomberg School's Department of Molecular Microbiology and Immunology. "It's like when you're weeding. Most current drugs just chop off the leaves, but the roots are still there. PZA gets at the roots. Learning how it does that may enable us to get rid of TB quicker and more permanently without relapse."

The new study, done in conjunction with Fudan University in Shanghai, found that PZA cuts off the energy production of Mycobacterium tuberculosis, killing the bacteria. It does this by disrupting the PanD, which, among other things, is crucial to synthesis of co-enzyme A, a molecule at the center of energy metabolism. When PanD is working correctly in a TB cell, it allows the cell to survive and persist despite a long course of treatment. Only PZA's unique ability to halt this process allows it to clear the dormant bacteria.

The researchers, who discovered another PZA target, Rspa, in recent years, say that PanD mutations are only found in a subset of TB bacteria resistant to PZA. The lab work done for the new study provides evidence that PanD is a new and distinct target for PZA, Zhang says.

PanD, Zhang says, is a promising finding because the enzyme is only present in bacteria like those found in TB and not in the cells of humans who contract the disease. It is always safer to attack a target that is only found in the dangerous organism and not in its host, he says.

In 2012, an estimated 8.6 million people worldwide developed TB and 1.3 million died from the disease. While the rate of new diagnoses is dropping, the number of drug-resistant cases is growing. When a patient is diagnosed with the lung disease, the course of treatment is six months of antibiotics. Researchers all over the world are trying to develop drugs that can work more quickly and without the toxic side effects common to all of the drugs in use.

PZA is the frontline treatment for TB. It is given to patients with both drug-susceptible and drug-resistant forms of the disease. All new drugs in development are used in conjunction with PZA.

Now that he understands the role that PZA plays on PanD and cells that persist long after treatment, Zhang says he plans to search for compounds that target PanD in the same way. The findings could have implications, he says, for developing drugs that target persistent organisms in other bacterial infections where dormant cells are known to re-emerge such as Lyme Disease, urinary tract infections and even cancer.


Story Source:

The above story is based on materials provided by Johns Hopkins University Bloomberg School of Public Health. Note: Materials may be edited for content and length.


Journal Reference:

  1. Wanliang Shi, Jiazhen Chen, Jie Feng, Peng Cui, Shuo Zhang, Xinhua Weng, Wenhong Zhang, Ying Zhang. Aspartate decarboxylase (PanD) as a new target of pyrazinamide in Mycobacterium tuberculosis. Emerging Microbes & Infections, 2014; 3 (8): e58 DOI: 10.1038/emi.2014.61

Cite This Page:

Johns Hopkins University Bloomberg School of Public Health. "Clues uncovered about how most important tuberculosis drug attacks its target." ScienceDaily. ScienceDaily, 13 August 2014. <www.sciencedaily.com/releases/2014/08/140813103938.htm>.
Johns Hopkins University Bloomberg School of Public Health. (2014, August 13). Clues uncovered about how most important tuberculosis drug attacks its target. ScienceDaily. Retrieved November 25, 2014 from www.sciencedaily.com/releases/2014/08/140813103938.htm
Johns Hopkins University Bloomberg School of Public Health. "Clues uncovered about how most important tuberculosis drug attacks its target." ScienceDaily. www.sciencedaily.com/releases/2014/08/140813103938.htm (accessed November 25, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Tuesday, November 25, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

From Popcorn To Vending Snacks: FDA Ups Calorie Count Rules

From Popcorn To Vending Snacks: FDA Ups Calorie Count Rules

Newsy (Nov. 25, 2014) — The US FDA is announcing new calorie rules on Tuesday that will require everywhere from theaters to vending machines to include calorie counts. Video provided by Newsy
Powered by NewsLook.com
Daily Serving Of Yogurt Could Reduce Risk Of Type 2 Diabetes

Daily Serving Of Yogurt Could Reduce Risk Of Type 2 Diabetes

Newsy (Nov. 25, 2014) — Need another reason to eat yogurt every day? Researchers now say it could reduce a person's risk of developing type 2 diabetes. Video provided by Newsy
Powered by NewsLook.com
Madagascar Working to Contain Plague Outbreak

Madagascar Working to Contain Plague Outbreak

AFP (Nov. 24, 2014) — Madagascar said Monday it is trying to contain an outbreak of plague -- similar to the Black Death that swept Medieval Europe -- that has killed 40 people and is spreading to the capital Antananarivo. Duration: 00:42 Video provided by AFP
Powered by NewsLook.com
Are Female Bosses More Likely To Be Depressed?

Are Female Bosses More Likely To Be Depressed?

Newsy (Nov. 24, 2014) — A new study links greater authority with increased depressive symptoms among women in the workplace. Video provided by Newsy
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