Macrophage induced Salmonella Typhimurium high-persister clones

S. Typhimurium persister populations were enriched for high-persister populations during serial passages of macrophage infection followed by persister isolation.After 7 rounds, we randomly picked 6 isolates and subjected these to WGS.The six isolates were clonal harboring the same 5 mutations.An in-frame deletion shortens a conserved protein with 5 amino acid and was shown to confer increased persistence. This deletion is also found in a small fraction of clinical Salmonella isolates.Another deletion fused two genes of an operon in-frame resulting in expression of a larger protein relevant for both persistenc and systemic infections in mice.In conclusion, during brief exposures to the host environment S. Typhimurium acquires distinct mutations resulting in novel allelic variants of proteins involved in persistence and virulence.