Final Report Summary - PERSIST (Bacterial Persistence)
The ERC-funded research project PERSIST has determined that randomly produced amounts of a signaling molecule can prompt a multidrug-tolerant state found in one in every million bacterial cells. Populations of many disease-causing bacteria contain ‘persisters’: slow-growing but genetically unchanged cells, which can resuscitate and multiply after antibiotic treatment. Such persisters are implicated in chronic and recurrent infections such as tuberculosis. Kenn Gerdes and his colleagues at Newcastle University, UK, and at the University of Copenhagen, Denmark showed that the mechanism behind persistence in Escherichia coli can be traced to the signaling molecule (p)ppGpp, which is known to initiate a drug-tolerant stress response in many different kinds of pathogenic bacteria. Levels of this molecule vary between cells, and the rare cells that produce (p)ppGpp amounts above a certain threshold grow slowly and resist antibiotics. Why some cells produce more (p)ppGpp than others remains unclear, but the authors propose a “microstarvation” model in which the cells with the least nutrients go into persistence. Other research groups have shown that many different kinds of bacteria also use this mechanism to become drug tolerant, arguing that drugs that inhibit (p)ppGpp synthesis may, in the future, become useful in the treatment of chronic and recurrent infections.