[WS10-1/ODP-207] Heterogeneity of intracellular ATP abundance in Salmonella Typhimurium induces diverse persisters
Antibiotic persistence is one of the causes for the antibiotic failure. The small subpopulation called persister is dormant and can survive against critical antibiotics without mutation. Many previous studies have shown that the persistence is induced by the energy repression such as ATP. In a clinically relevant environment, however, persister is reported to maintain a high level of ATP within host cells. We aimed to investigate the survival strategies of persistence in Salmonella Typhimurium (Stm) by analyzing the diversity of intracellular ATP abundance using a single-cell approach. To test both the growth activity and intracellular ATP abundance at single-cell level, we first constructed the Stm 14028 strain harboring both mCherry-expressing plasmid based on fluorescence dilution method and QUEEN-expressing plasmid as an ATP biosensor. We measured the histogram between mCherry and QUEEN intensity and monitored the responses in the presence of each antibiotic; ciprofloxacin or gentamicin. We detected high-ATP and low-ATP cells in non-growing cells, which suggests diverse persisters were induced in a clonal population. We also found two opposite antibiotic responses that ciprofloxacin increased subpopulation with a high-ATP abundance and gentamicin decreased ATP abundance. This suggests that the heterogeneity of intracellular ATP is important for diverse persisters to survive.