![]() The new molecules were more diverse than most available commercially, he said. ![]() "A few years ago, we found that through a series of organic chemistry steps we could change natural products into molecules that look very different from the parent compounds," Hergenrother said. ![]() These were the natural products of plants and microbes that the scientists had modified in the lab. Rather than using commercial chemical libraries, Hergenrother's group turned to its own collection of complex molecules. "Any drugs that work against them almost always are going through a special gateway, called a porin, that lets in amino acids and other compounds the bacteria need to live." "These microbes have an outer membrane that is basically impermeable to antibiotics or would-be antibiotics," Hergenrother said. coli, none of which led to a new drug, the researchers wrote. In 2007, for example, a large pharmaceutical company screened roughly 500,000 synthetic compounds for activity against E. The void of new antibiotics is not due to lack of effort. "Now, the bacteria are developing resistance to all of them." "We have a handful of classes of antibiotics that work against gram-negatives, but the last class was introduced 50 years ago, in 1968," Hergenrother said. The effort to find new antibiotics to combat these pathogens has failed again and again simply because almost all new drugs are unable to penetrate the gram-negative bacterial cell wall, Hergenrother said. Gram-negative bacteria include pathogenic strains of Escherichia coli, Acinetobacter, Klebsiella and Pseudomonas aeruginosa, all of which, according to the Centers for Disease Control and Prevention, are becoming "increasingly resistant to most available antibiotics." The modifications converted the drug into a broad-spectrum antibiotic that could also kill gram-negatives, the team reports. Led by University of Illinois chemistry professor Paul Hergenrother, the scientists tested their approach by modifying a drug that kills only gram-positive bacteria, which lack the rugged outer cell membrane that characterizes gram-negative microbes and makes them so difficult to combat. ![]()
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