The role of ATP pools in persister cell formation in (fluoro)quinolone-susceptible and -resistant strains of Salmonella enterica ser. Typhimurium

In this study, we investigated the reported dependence on the ATP pools for persister cell formation in fluoroquinolone-resistant variants of the facultative intracellular pathogen Salmonella enterica serovar Typhimurium. We compared the generation of persister cell populations after ciprofloxacin challenge of wildtype and a nalidixic acid-resistant variant of S. Typhimurium with reduced ciprofloxacin-susceptibility, as well as strains containing a deletion of the atp operon or harbouring the cloned atp genes. A gyrA mutation (D87Y) was found to contribute to increased stationary phase formation of persister cells in S. Typhimurium. However, in contrast to expectations from prior studies, while treatment with the ATP synthase poison arsenate showed the expected increase in persister cells surviving ciprofloxacin treatment, a more direct approach using a strain of Salmonella deleted for the atp operon showed severe reductions in persister cell formation. Persister cell formation was recovered after introduction of the cloned atp operon which restored the reduced ATP levels. These results suggest either an alternative explanation for previous studies, or that persister cell formation in Salmonella is differently regulated.