Small Molecules Bust Biofilms

Two small molecules that block the formation of life-threatening biofilms of gram-negative bacteria have been identified by chemists at the University of Wisconsin, Madison. Biofilms are drug-impervious bacterial communities that underlie a wide variety of chronic infections. Efforts to block biofilm formation with small molecules have focused largely on analogs of N-acyl L-homoserine lactones (AHLs), bacterial signaling molecules that regulate the chemical communication system (known as quorum sensing) that triggers biofilm formation in gram-negative bacteria. Helen E. Blackwell and coworkers at Wisconsin now have developed a facile and flexible solid-phase synthetic route to a wide range of AHL analogs (J. Am. Chem. Soc. 2005, 127, 12762). Two of these analogs (shown) strongly inhibit the formation of Pseudomonas aeruginosa biofilms, the root cause of often-fatal lung infections in cystic fibrosis sufferers. "By facilitating the production of focused combinatorial libraries of AHL analogs, our route should dramatically accelerate the discovery of new molecules that modulate quorum sensing and biofilm formation," Blackwell says.