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    Reduced persister cell formation in an ATP-synthase deficient mutant strain of Salmonella Typhimurium (2021)

    Art
    Vortrag
    Autoren
    Braetz, Sebastian (WE 7)
    Schwerk, Peter (WE 7)
    Thompson, Arthur
    Tedin, Karsten (WE 7)
    Fulde, Marcus (WE 7)
    Kongress
    Zoonoses 2021
    online, 13. – 15.10.2021
    Quelle
    Zoonoses 2021 - International Symposium on Zoonoses Research : joint meeting of the German Research Platform for Zoonoses and the Research Network Zoonotic Diseases : program and abstracts — Forschungsnetz zoonotische Infektionskrankheiten, German Research Platform for Zoonoses (Hrsg.)
    — S. 56
    Sprache
    Englisch
    Verweise
    URL (Volltext): https://evis.events/event/170/attachments/90/194/Zoonoses%202021%20-%20BoA_13.10.2021-2.pdf
    Kontakt
    Institut für Mikrobiologie und Tierseuchen

    Robert-von-Ostertag-Str. 7-13
    14163 Berlin
    +49 30 838 51843 / 66949
    mikrobiologie@vetmed.fu-berlin.de

    Abstract / Zusammenfassung

    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.