Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Wisconsin chemists find a new chink in TB’s armor

10.05.2004


The family of bacteria that causes tuberculosis (TB) and leprosy are notoriously sturdy. And although the diseases they cause have been held in check for the past 50 years by antibiotics, some strains are becoming increasingly resistant to existing therapy.



Now, however, a new chink has been found in the cellular armor that makes these infectious diseases difficult to treat. The discovery, reported today (May 9) in the online editions of the journal Nature Structural & Molecular Biology by a team of chemists and biochemists from the University of Wisconsin-Madison, opens the door to the development of a new family of antibiotics to treat diseases that still claim as many as 3 million lives annually worldwide.

"Most of the treatments we have for these diseases date from the 1950s," says Laura L. Kiessling, a UW-Madison professor of chemistry and the leader of the team reporting the new discovery. "Many traditional antibiotics don’t work against tuberculosis."


The bacteria that cause tuberculosis are literally tough as nails. With unique multilayered cell walls, the microbes resist easy treatment.

Current drug regimens typically last up to six months and require a mix of as many as six different drugs. Because the drugs cause unpleasant side effects, and because patients often feel better after a month or two, many people do not complete treatments, a phenomenon contributing to a worldwide epidemic of multidrug-resistant TB. Adding to the problem, in less developed countries where TB is most common, health care is spotty and drug supplies are frequently inadequate.

Kiessling and her colleagues, working with the support of the National Science Foundation, have detailed the workings of a key enzyme that the bacterium requires to maintain the integrity of its cell walls. Enzymes are proteins that initiate chemical reactions within plant and animal cells.

"We’ve figured out how this enzyme works. If you knock it out, the bacteria aren’t viable," Kiessling explains. "It’s an essential enzyme."

The TB microbe’s success and resistance to traditional drugs is attributed in large measure to its multilayered cell wall, composed of chicken wire-shaped molecules wrapped around an inner membrane. Atop that structure, are three more layers that further insulate the microbe from attack by traditional antibiotics.

The enzyme is required for the TB bacterium to build its cell wall. The enzyme, in turn, depends on a derivative of vitamin B2 to make a cell wall building block. The work published today by Kiessling’s group shows that the enzyme uses the vitamin in a new way, which also gives it a new biological role.

Detailing the interplay between vitamin B2 and the enzyme provides a blueprint for inhibitors of the enzymes that keep the bacterium’s cell walls intact. As a result, Kiessling’s group has effectively identified a target for drug manufactures interested in developing new antibiotics to combat TB and other diseases such as leprosy, which are caused by similar types of bacteria.

"Because we understand the mechanism better, we can design inhibitors of this enzyme," Kiessling says.

However, she notes that under the best circumstances, it takes years and many millions of dollars for new drugs to be developed. What’s more, she says, many major drug manufacturers are not actively pursuing the development of new antibiotics, despite growing resistance by microbes to antibiotics currently in use.

Tuberculosis, once commonly referred to as consumption, has a long history. Evidence of tubercular decay has been found in the bones of Egyptian mummies. It was identified by Hippocrates, the ancient Greek physician, as the most widespread and fatal disease of the ancient world. It has claimed many notable victims throughout history, including the poet John Keats, composer Frederick Chopin, playwright Anton Chekhov and writers Robert Louis Stevenson, Emily Bronte, D.H. Lawrence and George Orwell.

In addition to Kiessling, the authors of the Nature Structural & Molecular Biology paper include Michelle Soltero-Higgen and Todd D. Gruber of the UW-Madison Department of Biochemistry and Erin E. Carlson of the UW-Madison Department of Chemistry.


Terry Devitt (608) 262-8282, trdevitt@wisc.edu

Laura L. Kiessling | EurekAlert!
Further information:
http://www.wisc.edu/

More articles from Life Sciences:

nachricht Researchers identify potentially druggable mutant p53 proteins that promote cancer growth
09.12.2016 | Cold Spring Harbor Laboratory

nachricht Plant-based substance boosts eyelash growth
09.12.2016 | Fraunhofer-Institut für Angewandte Polymerforschung IAP

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Electron highway inside crystal

Physicists of the University of Würzburg have made an astonishing discovery in a specific type of topological insulators. The effect is due to the structure of the materials used. The researchers have now published their work in the journal Science.

Topological insulators are currently the hot topic in physics according to the newspaper Neue Zürcher Zeitung. Only a few weeks ago, their importance was...

Im Focus: Significantly more productivity in USP lasers

In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.

Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...

Im Focus: Shape matters when light meets atom

Mapping the interaction of a single atom with a single photon may inform design of quantum devices

Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

Researchers identify potentially druggable mutant p53 proteins that promote cancer growth

09.12.2016 | Life Sciences

Scientists produce a new roadmap for guiding development & conservation in the Amazon

09.12.2016 | Ecology, The Environment and Conservation

Satellites, airport visibility readings shed light on troops' exposure to air pollution

09.12.2016 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>