Population Dynamics Analysis of Ciprofloxacin-Persistent S. Typhimurium Cells in a Mouse Model for Salmonella Diarrhea.

In vivo, antibiotics are often surprisingly inefficient at eliminating bacterial pathogens. In the case of ciprofloxacin therapy in a Salmonella enterica subspecies 1 serovar Typhimurium (S. Typhimurium, S. Tm) mouse infection model, this has been traced to tolerant bacterial cells surviving in lymph node monocytes (i.e., classical dendritic cells). To analyze the growth characteristics of these persisters, we have developed a population dynamics approach using mixtures of wild-type isogenic tagged strains (WITS) and a computational model. Here, we are providing a detailed description of the inoculum, the infection experiments, the computational analysis of the WITS data, and a computer simulation for assessing the quality of the growth parameters of the persistent S. Typhimurium cells. This approach is generic. It may be adapted to any organ infected and to any bacterial pathogen, provided that tools exist for generating, retrieving, and quantifying isogenic tagged strains.