The recently emerged field of bacterial riboswitches may be a good hunting ground for effective targets against bacterial infection, according to a report by Yale researchers in the journal Chemistry and Biology.
Early studies to understand the malnutrition disease, beri beri, led to the identification of vitamin B1 (thiamine, inset, top), a nutrient found in brown rice but not polished white rice. The thiamine analog pyrithiamine (inset, bottom) has toxic effects in bacteria, fungi, and mammals - now shown to be caused in part by interactions with thiamine-specific riboswitches. Upper image is Aspergillus oryzae, a fungus that contains the riboswitch and is killed by pyrithiamine.
Riboswitches are RNA elements that control gene expression in essential metabolic pathways. Researchers in the laboratory of Ronald R. Breaker, the Henry Ford II Professor of Molecular, Cellular and Developmental Biology at Yale, showed that a riboswitch controlling vitamin B1 (thiamine) levels is disrupted in the presence of pyrithiamine, a toxic compound related to the vitamin.
Bacteria and fungi fail to grow in pyrithiamine and become resistant by acquiring mutations in their riboswitches. This work, in combination with the recently solved crystal structures of purine riboswitches, opens a path to the directed design of drugs targeting riboswitches for use as antibiotics.
Janet Rettig Emanuel | EurekAlert!
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