Using Engineered Bacteria to Characterize Infection Dynamics and Antibiotic Effects In Vivo

Abstract

Synthetic biology has focused on engineering microbes to synthesize useful products or to serve as living diagnostics and therapeutics. Here we utilize a host-derived Escherichia coli strain engineered with a genetic toggle switch as a research tool to examine invivo replicative states in a mouse model of chronic infection, and to compare invivo and invitro bacterial behavior. In contrast to the effect of antibiotics invitro, we find that the fraction of actively dividing bacteria remains relatively high throughout the course of a chronic infection invivo and increases in response to antibiotics. Moreover, the presence of non-dividing bacteria invivo does not necessarily lead to an antibiotic-tolerant infection, in contrast to expectations from invitro experiments. These results demonstrate the utility of engineered bacteria for querying pathogen behavior invivo, and the importance of validating invitro studies of antibiotic effects with invivo models.