Killing the survivors

Abstract

Antibiotic-tolerant, dormant variants of otherwise antibiotic-sensitive bacteria underlie many chronic and relapsing infections. A small molecule has been identified that can efficiently eradicate these persister cells. See Article p.365 Concerns about the ability of today's antibiotics to cope with future infections are compounded by the dual nature of the bacterial response to the drugs. Some bacteria develop genetic resistance, but others become tolerant, able to survive in the presence of antibiotics by forming dormant cells known as persisters in which the enzymatic targets of the antibiotics are inactive. Kim Lewis and colleagues sought compounds with the potential to kill persisters by corrupting targets within these energy-limited cells. They demonstrate that the acyldepsipeptide antibiotic ADEP4 activates ClpP protease and the cell's proteolytic machinery, killing persister cells by forcing them to degrade a range of cellular proteins. This is a potentially important result, suggesting that combining compounds such as ADEP4 with conventional antibiotics could provide new and robust strategies for the control of chronic infections.