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New drug lead fights bacteria that can be lethal by disrupting quorum sensing and biofilms

BUFFALO, N.Y. -- 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
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Contact: Ellen Goldbaum
goldbaum@buffalo.edu
716-645-5000 x1415
University at Buffalo
24-Jan-2003


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