Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New Drug Lead Fights Bacteria that can be Lethal by Disrupting Quorum Sensing and Biofilms

27.01.2003


Compound could lead to a new generation of antibiotics that battle resistance

University at Buffalo scientists have discovered a promising new drug lead that works by inhibiting the sophisticated bacterial communication system called quorum sensing.

The new compound is active against Pseudomonas aeruginosa, the gram-negative infection that strikes -- and usually kills -- cystic fibrosis patients and many others whose immune systems are compromised. The bacteria, like many others that have been routinely treated by antibiotics, have developed strains that are antibiotic-resistant.



The compound and the method the UB scientists used to develop it are described in the current (January 25, 2003) issue of Chemistry & Biology. The research also is discussed in a second article in the "Previews" section of the journal.

A patent application has been filed on the method of synthesis and the compound.

"With this work, we have taken a critical step toward inhibiting quorum sensing for clinical applications," said Hiroaki Suga, Ph.D., UB associate professor of chemistry and corresponding author on the paper.

Quorum sensing is the process by which bacterial cells "sense" that their numbers have reached a certain level, Suga explained, so that they then can mount an effective attack. The process gets switched on, he said, in response to the autoinducers that accumulate in bacterial cells as they begin reproducing.

Once the cells "sense" that a quorum has been reached, they begin to communicate, a process that in turn "throws the switch" for manufacturing virulence factors, such as biofilms.

These tough, layered, polysaccharide shells provide the bacteria with a nearly impenetrable, self-protective mechanism that makes it extremely difficult, and in some cases impossible, to fight with antibiotics.

"Underneath the protective biofilm, the cells are happily reproducing, damaging the tissue and producing toxins," said Suga.

Based on the structure of the quorum-sensing molecule, the autoinducer, the UB team synthesized a library of compounds. This approach then allowed the scientists to discover a subset of molecules that, like the natural autoinducer, activate quorum sensing.

"We then synthesized a small, focused library of quorum-sensing agonists," said Suga. "Surprisingly, this focused library yielded a quorum-sensing antagonist."

"It has been shown that knockout of the quorum-sensing genes in P. aeruginosa significantly reduced its virulence, so this cell-to-cell communication process is an interesting new drug target," he said.

By disrupting the communication process, he explained, the new compound could lead to drugs that will prevent the formation of biofilms, restoring the potency of antibiotic treatments and limiting the development of antibiotic resistance.

Since many other bacterial infections operate through quorum sensing, this molecule likely will boost research into methods to disrupt those as well, he added.

In addition, he said, compounds that inhibit quorum-sensing function differently from traditional antibiotics by attenuating pathogenicity, and therefore could prove very effective against resistant strains.

Suga explained that the quorum-sensing system is responsible for regulating a number of genes, including those that control the production of virulence factors.

"We now have a synthetic molecule that inhibits the master regulatory gene of quorum sensing," he said.

While Pseudomonas aeruginosa, which is ubiquitous in hospitals, has no effect on healthy people, it can be lethal to patients whose immune systems are compromised. In addition to cystic fibrosis patients, whose lungs become clogged with the bacteria, it infects patients receiving chemotherapy, burn patients, AIDS patients, those on ventilators, with catheters and others.

"The resistance problem demands development of a new type of drug, which differs in concept from traditional antibiotics," said Suga.

"Our work demonstrates a new strategy for identifying and designing antagonists to quorum sensing," he said. "We hope that additional studies in this direction lead us to discover even more potent quorum-sensing antagonists, thus generating a new type of antibiotic drug."

The paper is co-authored by Kristina M. Smith, who works in Suga’s lab and is doctoral candidate in the UB Department of Biological Sciences in the College of Arts and Sciences, and Yigong Bu, a former doctoral candidate at UB, who earned his doctorate from the UB Department of Chemistry.

Funding for the work was provided by the Interdisciplinary Research and Creative Activities Fund, Office of the Vice President for Research at UB.

Contact: Ellen Goldbaum, goldbaum@buffalo.edu
Phone: 716-645-5000 ext 1415
Fax: 716-645-3765

Ellen Goldbaum | University at Buffalo
Further information:
http://www.buffalo.edu/news/fast-execute.cgi/article-page.html?article=60440009

More articles from Life Sciences:

nachricht New switch decides between genome repair and death of cells
27.09.2016 | University of Cologne - Universität zu Köln

nachricht A blue stoplight to prevent runaway photosynthesis
27.09.2016 | National Institute for Basic Biology

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

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...

Im Focus: Complex hardmetal tools out of the 3D printer

For the first time, Fraunhofer IKTS shows additively manufactured hardmetal tools at WorldPM 2016 in Hamburg. Mechanical, chemical as well as a high heat resistance and extreme hardness are required from tools that are used in mechanical and automotive engineering or in plastics and building materials industry. Researchers at the Fraunhofer Institute for Ceramic Technologies and Systems IKTS in Dresden managed the production of complex hardmetal tools via 3D printing in a quality that are in no way inferior to conventionally produced high-performance tools.

Fraunhofer IKTS counts decades of proven expertise in the development of hardmetals. To date, reliable cutting, drilling, pressing and stamping tools made of...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

European Health Forum Gastein 2016 kicks off today

28.09.2016 | Event News

Laser use for neurosurgery and biofabrication - LaserForum 2016 focuses on medical technology

27.09.2016 | Event News

Experts from industry and academia discuss the future mobile telecommunications standard 5G

23.09.2016 | Event News

 
Latest News

New imaging technique in Alzheimer’s disease - opens up possibilities for new drug development

28.09.2016 | Medical Engineering

Innovate coating extends the life of materials for industrial use

28.09.2016 | Materials Sciences

Blockchain Set to Transform the Financial Services Market

28.09.2016 | Business and Finance

VideoLinks
B2B-VideoLinks
More VideoLinks >>>