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 Millions through license revenues
27.04.2017 | Rheinische Friedrich-Wilhelms-Universität Bonn

nachricht New High-Performance Center Translational Medical Engineering
26.04.2017 | Fraunhofer ITEM

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: Making lightweight construction suitable for series production

More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.

Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...

Im Focus: Wonder material? Novel nanotube structure strengthens thin films for flexible electronics

Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.

"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Fighting drug resistant tuberculosis – InfectoGnostics meets MYCO-NET² partners in Peru

28.04.2017 | Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

 
Latest News

Wireless power can drive tiny electronic devices in the GI tract

28.04.2017 | Medical Engineering

Ice cave in Transylvania yields window into region's past

28.04.2017 | Earth Sciences

Nose2Brain – Better Therapy for Multiple Sclerosis

28.04.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>