Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Potent toxin reveals new antibiotic resistance mechanism

12.09.2003


One of the great frustrations of modern medicine is the creeping ability of pathogenic microbes to develop resistance to the antibiotics we throw at them.



More and more, microbes are able to eliminate, modify and sequester the toxic molecules that make up the arsenal of antibiotics that humans use to treat infection, making once-miraculous drugs increasingly impotent. Now, adding to the mix of devices dangerous microbes deploy to evade destruction by antibiotics, scientists have discovered another way pathogens escape from the most potent drugs: self-sacrifice.

It is the equivalent of the courageous soldier throwing himself on a grenade, says Jon S. Thorson, a University of Wisconsin-Madison professor of pharmacy and the senior author of a paper describing the newfound method of antibiotic resistance published in this week’s (Sept. 12) edition of the journal Science.


"It is a new paradigm for resistance," says Thorson. "It points to the fact that bacteria continue to find new routes to evade these drugs."

The discovery was made by Thorson and colleagues John B. Biggins and Kenolisa C. Onwueme of the Sloan-Kettering Division, Joan and Sanford A. Weill Graduate School of Medical Sciences, Cornell University Cancer Center. Biggins is now at the UW-Madison School of Pharmacy.

The new finding was made using a highly potent anticancer agent known as an enediyne. Enediynes are a class of anti-tumor antibiotics that work by shredding DNA and disrupting the ability of a cell - such as cancer cell or a unicellular organism like a bacterium - to function and reproduce. They rank among the most potent naturally occurring antibiotics, and only a few molecules are required to destroy a cell.

In nature, soil bacteria use enediynes to create a buffer, a very localized environment free from competing microbes, which could overwhelm the slow-growing enediyne-producing bugs. But to survive in the toxic environment it creates, the microbe must have a way to survive its own poisons.

This is especially true, Thorson says, if one of the toxic molecules a bacterium secretes is soaked up by the bacterium itself. To protect itself, the bacterium quickly deploys a protein that intercepts the misdirected enediyne before it finds and destroys the organism’s DNA.

"Instead of cleaving DNA, the enediyne cleaves the protein and thereby inactivates itself," says Thorson. "By detonating its ’warhead’ to cleave the protein instead of the DNA, the cell is preserved. It’s somewhat inefficient, but at least the cell survives."

Over time, many antibiotic-producing microbes have evolved a variety of ways of not succumbing to the toxins they use to keep competitors at bay. But these methods of evading their own chemical warfare agents tend to be shared among bacteria, says Thorson, and are at the root of antibiotic resistance among the pathogenic bacteria that also borrow the defense mechanisms.

Scientists have long known that bacteria can thwart antibiotics by rearranging their chemistry to keep a drug from binding to a cell. What’s more, bacteria have learned how to clean house by quickly pumping antibiotic molecules out of affected cells. They also have acquired the trick of making molecular ’sponges,’ proteins that bind to antibiotics and take the drugs out of the game before they can do their lethal work.

The new mechanism found by Thorson’s group does not bode well for the fight against dangerous and sometimes deadly bacteria.

"Many of our drugs are coming from soil bacteria like these," Thorson says referring to the enediyne-producing bacteria with which he works. "This is the first known example of this kind of self-sacrifice mechanism for resistance. It points to the fact that bacteria continue to find new routes to evade these (antibiotic) molecules."

It would be surprising, Thorson argues, for this new mechanism to be unique to the enediyne-producing bacteria.

"One of the questions we’ve asked ourselves is, ’[Is] this a once-in-a-blue-moon discovery - or will this mechanism be found in other organisms?’ Since nature usually sticks with what works, I would not be surprised if we see this mechanism pop up again."


###
The work conducted by the Wisconsin team was funded in part by the National Institutes of Health.

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

Jon S. Thorson | EurekAlert!
Further information:
http://www.wisc.edu/

More articles from Health and Medicine:

nachricht Custom-tailored strategy against glioblastomas
26.09.2016 | Rheinische Friedrich-Wilhelms-Universität Bonn

nachricht New leukemia treatment offers hope
23.09.2016 | King Abdullah University of Science and Technology

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

Im Focus: First-Ever 3D Printed Excavator Project Advances Large-Scale Additive Manufacturing R&D

Heavy construction machinery is the focus of Oak Ridge National Laboratory’s latest advance in additive manufacturing research. With industry partners and university students, ORNL researchers are designing and producing the world’s first 3D printed excavator, a prototype that will leverage large-scale AM technologies and explore the feasibility of printing with metal alloys.

Increasing the size and speed of metal-based 3D printing techniques, using low-cost alloys like steel and aluminum, could create new industrial applications...

Im Focus: New welding process joins dissimilar sheets better

Friction stir welding is a still-young and thus often unfamiliar pressure welding process for joining flat components and semi-finished components made of light metals.
Scientists at the University of Stuttgart have now developed two new process variants that will considerably expand the areas of application for friction stir welding.
Technologie-Lizenz-Büro (TLB) GmbH supports the University of Stuttgart in patenting and marketing its innovations.

Friction stir welding is a still-young and thus often unfamiliar pressure welding process for joining flat components and semi-finished components made of...

Im Focus: First quantum photonic circuit with electrically driven light source

Optical quantum computers can revolutionize computer technology. A team of researchers led by scientists from Münster University and KIT now succeeded in putting a quantum optical experimental set-up onto a chip. In doing so, they have met one of the requirements for making it possible to use photonic circuits for optical quantum computers.

Optical quantum computers are what people are pinning their hopes on for tomorrow’s computer technology – whether for tap-proof data encryption, ultrafast...

Im Focus: OLED microdisplays in data glasses for improved human-machine interaction

The Fraunhofer Institute for Organic Electronics, Electron Beam and Plasma Technology FEP has been developing various applications for OLED microdisplays based on organic semiconductors. By integrating the capabilities of an image sensor directly into the microdisplay, eye movements can be recorded by the smart glasses and utilized for guidance and control functions, as one example. The new design will be debuted at Augmented World Expo Europe (AWE) in Berlin at Booth B25, October 18th – 19th.

“Augmented-reality” and “wearables” have become terms we encounter almost daily. Both can make daily life a little simpler and provide valuable assistance for...

Im Focus: Artificial Intelligence Helps in the Discovery of New Materials

With the help of artificial intelligence, chemists from the University of Basel in Switzerland have computed the characteristics of about two million crystals made up of four chemical elements. The researchers were able to identify 90 previously unknown thermodynamically stable crystals that can be regarded as new materials. They report on their findings in the scientific journal Physical Review Letters.

Elpasolite is a glassy, transparent, shiny and soft mineral with a cubic crystal structure. First discovered in El Paso County (Colorado, USA), it can also be...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Paper – Panacea Green Infrastructure?

30.09.2016 | Event News

HLF: From an experiment to an establishment

29.09.2016 | Event News

European Health Forum Gastein 2016 kicks off today

28.09.2016 | Event News

 
Latest News

First-Ever 3D Printed Excavator Project Advances Large-Scale Additive Manufacturing R&D

30.09.2016 | Materials Sciences

New Technique for Finding Weakness in Earth’s Crust

30.09.2016 | Earth Sciences

Cells migrate collectively by intermittent bursts of activity

30.09.2016 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>