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Blinding Bacteria to Nutrient Deficiency Boosts Sensitivity to Antibiotics

Preventing pathogenic bacteria from sensing nutrient starvation may present a new therapeutic approach to increasing antibiotic efficacy and preventing drug resistance, researchers claim. A team led by McGill University investigators has found that blocking an active mechanism used by bacteria to respond to starvation by slowing their growth significantly reduces the natural tolerance to antibiotics that infectious organisms develop when nutrient supplies become low.

Scientists have largely assumed that antibiotic resistance in nutrient-deprived bacteria occurs passively as the starved cells stop growing and the antibiotic target is inactivated. However, Pradeep K. Singh, Ph.D., Dao Nguyen, Ph.D., and colleagues now report that antibiotic tolerance resulting in nutrient-starved P. aeuriginosa and biofilm cultures is in fact mediated by an active protective mechanism controlled by the starvation-signaling stringent response (SR). Their in vitro and in vivo studies showed that inactivating this protective mechanism sensitized biofilms to different classes of antibiotics, and significantly improved the effects of antibiotic treatment in mouse models of infection.

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