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By speaking the language of bacteria, researchers from the State University of New York at Buffalo have made a critical advance in the development of what could be a new class of antibiotics. Such drugs could eventually combat a host of currently incurable infections-including those caused by Pseudomonas aeruginosa, a bacterium that chronically infects nearly 70 percent of cystic-fibrosis patients.

Most antibiotics block bacteria’s ability to synthesize proteins or cell membranes, says biochemist Hiroaki Suga, who led the effort, but “our approach targets a completely different system.” That system is a means of communication that many species of bacteria use to gang up on their hosts. Alone, these bacteria are often harmless and susceptible to regular antibiotics. But once they reach a critical density and begin to communicate through chemicals they emit, they cooperate to boost their virulence and evade traditional treatments by, for example, forming slimy biofilms.

Previous efforts to develop drugs that disrupt bacterial communication have focused on naturally occurring chemicals. Suga instead synthesized a library of molecules from scratch by tinkering with the structure of one of the communication chemicals found in Pseudomonas. Several of Suga’s new molecules blocked the bacteria’s conversation; such molecules could be used with conventional antibiotics to more effectively target the microbes.

Suga’s molecules aren’t strong enough to be used as drugs, says the University of Texas at Austin’s Walter Fast, a medicinal chemist, but their development marks an important step forward. And, Fast says, “Hiro’s approach is definitely generalizable to other bacteria.” Suga has filed a patent on the technology and is fielding corporate interest. “We hope to discover more potent antagonists,” he says, “so that we can get closer to developing a real drug in the future.” Such drugs could bust up even the toughest bacterial gangs.

Photo courtesy of Chemistry & Biology, vol 10, no 1, 2003, pp81-89, Smith et al: “Induction and Inhibition of Pseudomonas aeruginosa…”1 figure.

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