Robert-von-Ostertag-Str. 7-13
14163 Berlin
+49 30 838 51843 / 66949
mikrobiologie@vetmed.fu-berlin.de
Bacterial persisters are drug-tolerant cells, characterized as slow growing, with reduced metabolic activity and an extraordinary tolerance against antimicrobial agents, despite the lack of genetic resistance mechanisms. It was proposed that reduced ATP levels is a key factor contributing to bacterial
persistence, as low ATP levels result in reduced target activity of the antibiotics and, thus, ultimately protect the bacteria against lethal cellular damage.
Here, we demonstrate that a Salmonella Typhimurium strain lacking the entire atp synthase operon, forms less persister cells after exposure to ciprofloxacin in comparison to its parental wild-type. As reduced ATP levels lead to increased oxygen consumption which can contribute to reactive oxygen
species (ROS) formation, we performed a set of experiments to investigate the mechanisms of the association between the redox status of the bacterial cell, the amount of ROS formation under low ATP levels, and the level of persister cells under highly standardized conditions.
Our results indicate that the atp operon mutant has increased accumulation of NAD(P)H, which supports flavin reductase reactions to reduce ferrous iron to ferric iron. This in turn, increases the Fenton reaction and the formation of hydroxyl radicals, which in turn increases the susceptibility and bactericidal effects of ciprofloxacin.