Featured Research

from universities, journals, and other organizations

New Chemical Can Kill Latent Tuberculosis Bacteria, Study Shows

Date:
March 18, 2008
Source:
New York- Presbyterian Hospital/Columbia University Medical Center
Summary:
Success in the laboratory suggests that a new compound can point the way to preventing active tuberculosis in people infected with the latent form of the bacterium. A drug with such properties could also be useful in treating people who already have tuberculosis by shortening the lengthy treatment period. The discovery also points to new ways of thinking about fighting bacterial infection, which is becoming increasingly resistant to traditional antibiotics.

Success in the laboratory suggests that a new compound can point the way to preventing active tuberculosis in people infected with the latent form of the bacterium, says a team led by researchers at Weill Cornell Medical College in New York City. A drug with such properties could also be useful in treating people who already have tuberculosis by shortening the lengthy treatment period. The discovery also points to new ways of thinking about fighting bacterial infection, which is becoming increasingly resistant to traditional antibiotics.

"With each new case of antibiotic resistance, doctors are losing ground against Mycobacterium tuberculosis and other infectious diseases," explains the study's senior author Dr. Carl Nathan, chairman of Microbiology and Immunology and the R.A. Rees Pritchett Professor of Microbiology at Weill Cornell Medical College. "This new approach fights the pathogen in a way that's different from conventional antibiotics. For what may be the first time, we have found compounds that only kill M. tuberculosis when they are not dividing. This lack of replication is a characteristic of latent bacteria, which are tough to eradicate with existing antibiotics and ultimately play a huge role in the epidemic's spread."

It's tough to overestimate TB's impact on public health. According to the World Health Organization, the lung infection kills over 1.6 million people worldwide each year.

About a third of the world's people are also thought to be infected with latent or non-replicating M. tuberculosis. In about 5 to 10 percent of these individuals, the latent bacteria eventually begin to replicate, causing active disease. On average, each person with active TB is thought to spread the infection to between 9 and 20 other people, experts say.

"That means that killing latent M. tuberculosis is one of the keys to curtailing or eliminating TB as a disease," Dr. Nathan says. "Antibiotic research has typically focused on killing rapidly dividing bacteria. But with antibiotic resistance rising, that no longer seems like a winning strategy. The long duration of treatment required for curing TB may reflect the fact that some of the bacteria remain non-dividing even during clinically active disease."

With current drugs, it can take six months to eradicate most non-dividing bacteria, and adherence to that long a regimen is difficult for many patients. But if they stop treatment prematurely, drug-resistant bacteria can emerge. Those bacteria are even harder to eradicate if treatment is resumed, and in the meantime, the resistant strain may have also been passed on to others.

In their experiments, the Weill Cornell researchers focused on a bacterial enzyme called dihydrolipoamide acetyltransferase (DlaT). "DlaT's main job is to help M. tuberculosis get energy from nutrients. But when the bacterium is under stress, it also uses the enzyme to defend itself against oxidative damage from human immune cells, such as macrophages," explains study lead author Dr. Ruslana Bryk, assistant research professor in the Department of Microbiology and Immunology at Weill Cornell Medical College.

The team's work in guinea pigs revealed that DlaT is crucial to triggering active TB disease. "So we screened 15,000 compounds to find chemicals that might inhibit DlaT," Dr. Bryk says. The researchers discovered one such compound from a class of chemicals called rhodanines. Their collaborators at deCODE Chemistry then synthesized over 1,000 different variants until the Weill Cornell team found several that can enter and selectively kill non-dividing M. tuberculosis.

"We believe that these DlaT inhibitors probably target additional mechanisms that non-dividing M. tuberculosis needs to survive, and we are currently investigating that possibility," Dr. Nathan says. "We also believe that these compounds work in synergy with human immune responses and the chemical environment inside the host to kill latent bacteria."

The inhibitors described in the paper are surely not the only ones with the ability to kill non-dividing M. tuberculosis selectively. "This was really a proof-of-principle effort to show that targeting non-dividing bacteria was feasible," Dr. Nathan explains. "In recent work supported by the Bill and Melinda Gates Foundation, we have since found additional compounds that appear to kill non-dividing M. tuberculosis selectively."

"As a parent, a citizen and an occasional patient, I worry about losing the hard-fought gains we've made against infectious disease," Dr. Nathan says. "When traditional antibiotics work, treating TB, pneumonia and other bacterial diseases seems routine. When they don't work -- as is happening now with growing frequency -- these infections become emergencies. The growing crisis of microbial resistance demands innovative new approaches. We hope this work will encourage more scientists that such innovations are worth seeking."

The new findings are published in the March 12 online issue of the journal Cell Host & Microbe.

This work was funded by the U.S. National Institutes of Health and the Abby and Howard P. Milstein Program in Chemical Biology of Infectious Disease at Weill Cornell. The Weill Cornell Department of Microbiology and Immunology is supported by the William Randolph Hearst Foundation.

Co-researchers include Dr. Benjamin Gold, Dr. Sabine Ehrt, Dr. Kyu Rhee, Dr. Gang Lin, Aditya Venugopal, Omar Vandal, Xiuju Jiang and Jean Schneider -- all of Weill Cornell Medical College; Dr. Jasbir Singh, Dr. Raghu Samy, Dr. Krzysztof Pupek, Dr. Hua Cao, Dr. Carmen Popescu and Dr. Mark Gurney, of deCODE Chemistry Inc., Woodbridge, Ill.; Dr. Srinivas Hotha and Dr. Joseph Cherian, formerly of The Rockefeller University, New York City; Dr. Lan Ly of Texas A&M University Health Science Center, College Station; and Dr. Paul J. Converse of Johns Hopkins University, Baltimore.


Story Source:

The above story is based on materials provided by New York- Presbyterian Hospital/Columbia University Medical Center. Note: Materials may be edited for content and length.


Cite This Page:

New York- Presbyterian Hospital/Columbia University Medical Center. "New Chemical Can Kill Latent Tuberculosis Bacteria, Study Shows." ScienceDaily. ScienceDaily, 18 March 2008. <www.sciencedaily.com/releases/2008/03/080314112637.htm>.
New York- Presbyterian Hospital/Columbia University Medical Center. (2008, March 18). New Chemical Can Kill Latent Tuberculosis Bacteria, Study Shows. ScienceDaily. Retrieved October 22, 2014 from www.sciencedaily.com/releases/2008/03/080314112637.htm
New York- Presbyterian Hospital/Columbia University Medical Center. "New Chemical Can Kill Latent Tuberculosis Bacteria, Study Shows." ScienceDaily. www.sciencedaily.com/releases/2008/03/080314112637.htm (accessed October 22, 2014).

Share This



More Health & Medicine News

Wednesday, October 22, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

CDC Revamps Ebola Guidelines After Criticism

CDC Revamps Ebola Guidelines After Criticism

Newsy (Oct. 21, 2014) The Centers for Disease Control and Prevention have issued new protocols for healthcare workers interacting with Ebola patients. Video provided by Newsy
Powered by NewsLook.com
WHO: Ebola Vaccine Trials to Start a in January

WHO: Ebola Vaccine Trials to Start a in January

AP (Oct. 21, 2014) Tens of thousands of doses of experimental Ebola vaccines could be available for "real-world" testing in West Africa as soon as January as long as they are deemed safe in soon to start trials, the World Health Organization said Tuesday. (Oct. 21) Video provided by AP
Powered by NewsLook.com
First-Of-Its-Kind Treatment Gives Man Ability To Walk Again

First-Of-Its-Kind Treatment Gives Man Ability To Walk Again

Newsy (Oct. 21, 2014) A medical team has for the first time given a man the ability to walk again after transplanting cells from his brain onto his severed spinal cord. Video provided by Newsy
Powered by NewsLook.com
CDC Issues New Ebola Guidelines for Health Workers

CDC Issues New Ebola Guidelines for Health Workers

Reuters - US Online Video (Oct. 21, 2014) The U.S. Centers for Disease Control and Prevention has set up new guidelines for health workers taking care of patients infected with Ebola. Linda So reports. Video provided by Reuters
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