Analysis of Salmonella Persister Population Sizes, Dynamics of Gut Luminal Seeding, and Plasmid Transfer in Mouse Models of Salmonellosis.

A previously unappreciated link between persisters and the emergence and spread of antibiotic resistance has been recently established. The bulk of this research has been conducted in vitro, but some studies are beginning to elucidate the importance of persister reservoirs in both antibiotic treatment failure and the spread of antibiotic resistance using in vivo models. In order to further this research, careful analyses of the mechanisms of persister reservoir formation as well as the dynamics of persister survival and postantibiotic regrowth are of importance. Here, we present a mouse model to quantitatively study Salmonella persisters in vivo. By using neutral unique sequence barcodes, we describe the quantitative analysis of rare events (aka bottlenecks) associated with persister reservoir formation, survival, and reseeding of the gut lumen. This provides quantitative data for persister-fueled plasmid transfer in vivo. Although this chapter describes analysis of Salmonella persisters in a mouse model, these concepts can be applied to any experimental system provided that tractable experimental systems are present.