Featured Research

from universities, journals, and other organizations

Antibiotics observed attacking tuberculosis: Mass spectrometry shows scientists how antibiotics function inside living bacteria

Date:
November 1, 2012
Source:
Weill Cornell Medical College
Summary:
Researchers report that mass spectrometry, a tool currently used to detect and measure proteins and lipids, can also now allow biologists to "see" for the first time exactly how drugs work inside living cells to kill infectious microbes. As a result, scientists may be able to improve existing antibiotics and design new, smarter ones to fight deadly infections, such as tuberculosis.

Weill Cornell Medical College researchers report that mass spectrometry, a tool currently used to detect and measure proteins and lipids, can also now allow biologists to "see" for the first time exactly how drugs work inside living cells to kill infectious microbes. As a result, scientists may be able to improve existing antibiotics and design new, smarter ones to fight deadly infections, such as tuberculosis.

Related Articles


The new study was published in the Nov. 1 early online edition of Science.

"The development of antibiotics has been stalled for several decades and many infectious microbes have become drug-resistant," says the study's senior investigator, Dr. Kyu Y. Rhee, an infectious disease expert who is an associate professor of medicine in the Division of Infectious Diseases and associate professor of microbiology and immunology at Weill Cornell Medical College. "We must restock the antibiotic pipeline and our study findings provide a powerful new approach for doing just that."

The need to develop new antibiotics is perhaps nowhere more pressing than for the treatment of tuberculosis, TB, which is the single leading bacterial cause of death worldwide, and with the emergence of now total drug resistance, an unchecked global public health emergency.

"Current TB treatments are long and complex, lasting a minimum of six months, and often resulting in treatment failures and the paradoxical emergence of multi-drug resistance," says Dr. Rhee, who is also an associate attending physician at NewYork-Presbyterian Hospital/Weill Cornell Medical Center. "We are still using the antibiotics that were first developed for TB about 50 years ago."

Most TB drugs -- as well as antibiotics for other infections -- were developed through a combination of empirical approaches, Dr. Rhee explains. "However, it had been impossible to know what the drug was doing inside the bacteria."

That situation has now changed. Dr. Rhee and his colleagues, who include investigators from the National Institutes of Health, applied modern technologies that stem from use of mass spectrometry to directly visualize what happens when these drugs infiltrate TB cells. They can "watch," at a basic biochemical level, what happens to both the antibiotic agent and infecting bacteria over time after the drug is administered.

Mass spectrometry, simply stated, is a tool that weighs individual molecules as a way to identify them. It was first used in physics, but has expanded to many disciplines to help scientists identify molecules and determine the quantity of each kind in gases, liquids, as well as solids. Advances in mass spectrometry have made it possible for biologists to leverage the tool in the last few years, and, with this study, evaluate the intracellular fates and actions of small drug molecules.

This study is the first to show mass spectrometry can also be adapted to understand the action of antibiotics on living, intact bacterial cells.

In the study, Dr. Rhee's research team exposed TB to para-aminosalicylic acid (PAS), which was developed more than 50 years ago, and is still part of the multi-drug regimen used to treat resistant TB. It is the second oldest TB drug on the market.

The drug was thought to work by inhibiting an enzyme used by bacteria to synthesize folates, an essential class of nutrients that humans acquire by eating, but bacteria must make on their own. "Many thus believed that the drug interfered with folate synthesis in the TB bacterium by functioning as an occlusive plug that blocked this pathway," says Dr. Rhee.

However, researchers actually found, while it is true PAS prevents the utilization of the natural precursors used to synthesize folates, once inside TB, PAS itself also turns toxic. "PAS is an agent that uses the TB cell's machinery to turn it into a poison. Thus, it doesn't simply kill the cell by stopping its food supply, it also morphs into a lethal drug," Dr. Rhee says.

The researchers also tested a different drug, sulfonamide (sulfa), which is an 80-year-old class of antibacterial agents known to defeat many infections, but not TB successfully.

"Scientists thought sulfa didn't penetrate TB cells, but we witnessed, using mass spectrometry, that it did, in fact, enter the bacteria. But that once inside, TB bacteria were able to degrade the drug," Dr. Rhee says. This finding suggests to researchers that it might be possible to modify the sulfa molecule so that it can withstand degradation by TB bacteria.

"Both of these findings were completely unexpected," says Dr. Rhee. "The study findings show us that sometimes there is a profound disconnect between what we think a drug is doing and how it actually works inside cells."

"The power of mass spectrometry is now evident, and we can't wait to use it to test all of the current cocktail of drugs used to treat TB to find ways to improve them," Dr. Rhee says. "Best of all will be the use of this tool to design and test the much-needed next generation of effective anti-TB agents."


Story Source:

The above story is based on materials provided by Weill Cornell Medical College. Note: Materials may be edited for content and length.


Cite This Page:

Weill Cornell Medical College. "Antibiotics observed attacking tuberculosis: Mass spectrometry shows scientists how antibiotics function inside living bacteria." ScienceDaily. ScienceDaily, 1 November 2012. <www.sciencedaily.com/releases/2012/11/121101141220.htm>.
Weill Cornell Medical College. (2012, November 1). Antibiotics observed attacking tuberculosis: Mass spectrometry shows scientists how antibiotics function inside living bacteria. ScienceDaily. Retrieved December 18, 2014 from www.sciencedaily.com/releases/2012/11/121101141220.htm
Weill Cornell Medical College. "Antibiotics observed attacking tuberculosis: Mass spectrometry shows scientists how antibiotics function inside living bacteria." ScienceDaily. www.sciencedaily.com/releases/2012/11/121101141220.htm (accessed December 18, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Thursday, December 18, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Kids Die While Under Protective Services

Kids Die While Under Protective Services

AP (Dec. 18, 2014) As part of a six-month investigation of child maltreatment deaths, the AP found that hundreds of deaths from horrific abuse and neglect could have been prevented. AP's Haven Daley reports. (Dec. 18) Video provided by AP
Powered by NewsLook.com
UN: Up to One Million Facing Hunger in Ebola-Hit Countries

UN: Up to One Million Facing Hunger in Ebola-Hit Countries

AFP (Dec. 17, 2014) Border closures, quarantines and crop losses in West African nations battling the Ebola virus could lead to as many as one million people going hungry, UN food agencies said on Wednesday. Duration: 00:52 Video provided by AFP
Powered by NewsLook.com
When You Lose Weight, This Is Where The Fat Goes

When You Lose Weight, This Is Where The Fat Goes

Newsy (Dec. 17, 2014) Can fat disappear into thin air? New research finds that during weight loss, over 80 percent of a person's fat molecules escape through the lungs. Video provided by Newsy
Powered by NewsLook.com
Why Your Boss Should Let You Sleep In

Why Your Boss Should Let You Sleep In

Newsy (Dec. 17, 2014) According to research out of the University of Pennsylvania, waking up for work is the biggest factor that causes Americans to lose sleep. 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