Role of the stringent response in antibiotic tolerance of Escherichia coli

Abstract

The stringent response is a near-universal bacterial adaptation system control mediated by accumulation of two guanine nucleotides ppGpp and pppGpp, collectively known as (p)ppGpp. The response monitors several environmental stress inputs, such as nutrient limitation and heat shock and remodels bacterial physiology in order to overcome the challenges. In Echerichia coli (p)ppGpp levels controlled by two enzymes – RelA and SpoT, the namesakes of RelA SpoT Homologue (RSH) protein family. The stringent response is associated to induction of virulence, antibiotic resistance and was recently suggested to be the driving force behind the formation of so-called persister cells – antibiotictolerant phenotypic variants in antibiotic-sensitive population. Since drug resistance and tolerance constitute a significant public health threat, understanding the connection amongst (p)ppGpp, antibiotic treatment and persistence is of great importance.