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 Catalysts for climate protection
19.08.2019 | Fraunhofer-Institut für Grenzflächen- und Bioverfahrenstechnik IGB

nachricht From the tiny testes of flies, new insight into how genes arise
19.08.2019 | Rockefeller University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: A miniature stretchable pump for the next generation of soft robots

Soft robots have a distinct advantage over their rigid forebears: they can adapt to complex environments, handle fragile objects and interact safely with humans. Made from silicone, rubber or other stretchable polymers, they are ideal for use in rehabilitation exoskeletons and robotic clothing. Soft bio-inspired robots could one day be deployed to explore remote or dangerous environments.

Most soft robots are actuated by rigid, noisy pumps that push fluids into the machines' moving parts. Because they are connected to these bulky pumps by tubes,...

Im Focus: Vehicle Emissions: New sensor technology to improve air quality in cities

Researchers at TU Graz are working together with European partners on new possibilities of measuring vehicle emissions.

Today, air pollution is one of the biggest challenges facing European cities. As part of the Horizon 2020 research project CARES (City Air Remote Emission...

Im Focus: Self healing robots that "feel pain"

Over the next three years, researchers from the Vrije Universiteit Brussel, University of Cambridge, École Supérieure de Physique et de Chimie Industrielles de la ville de Paris (ESPCI-Paris) and Empa will be working together with the Dutch Polymer manufacturer SupraPolix on the next generation of robots: (soft) robots that ‘feel pain’ and heal themselves. The partners can count on 3 million Euro in support from the European Commission.

Soon robots will not only be found in factories and laboratories, but will be assisting us in our immediate environment. They will help us in the household, to...

Im Focus: Scientists create the world's thinnest gold

Scientists at the University of Leeds have created a new form of gold which is just two atoms thick - the thinnest unsupported gold ever created.

The researchers measured the thickness of the gold to be 0.47 nanometres - that is one million times thinner than a human finger nail. The material is regarded...

Im Focus: Study on attosecond timescale casts new light on electron dynamics in transition metals

An international team of scientists involving the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) in Hamburg has unraveled the light-induced electron-localization dynamics in transition metals at the attosecond timescale. The team investigated for the first time the many-body electron dynamics in transition metals before thermalization sets in. Their work has now appeared in Nature Physics.

The researchers from ETH Zurich (Switzerland), the MPSD (Germany), the Center for Computational Sciences of University of Tsukuba (Japan) and the Center for...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

The power of thought – the key to success: CYBATHLON BCI Series 2019

16.08.2019 | Event News

4th Hybrid Materials and Structures 2020 28 - 29 April 2020, Karlsruhe, Germany

14.08.2019 | Event News

What will the digital city of the future look like? City Science Summit on 1st and 2nd October 2019 in Hamburg

12.08.2019 | Event News

 
Latest News

Stanford builds a heat shield just 10 atoms thick to protect electronic devices

19.08.2019 | Information Technology

Researchers demonstrate three-dimensional quantum hall effect for the first time

19.08.2019 | Physics and Astronomy

Catalysts for climate protection

19.08.2019 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>