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    Salmonella central carbon metabolism enhances bactericidal killing by fluoroquinolone antibiotics (2022)

    Art
    Poster
    Autoren
    Braetz, Sebastian (WE 7)
    Schwerk, Peter (WE 7)
    Thompson, Arthur
    Tedin, Karsten (WE 7)
    Fulde, Marcus (WE 7)
    Kongress
    Zoonoses 2022 - International Symposium on Zoonoses Research
    Berlin, 05. – 07.10.2022
    Quelle
    Antimicrobial agents and chemotherapy
    Bandzählung: 66
    Heftzählung: 7
    Seiten: Artikel e0234421
    ISSN: 1098-6596
    Sprache
    Englisch
    Verweise
    URL (Volltext): https://journals.asm.org/doi/10.1128/aac.02344-21
    DOI: 10.1128/aac.02344-21
    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

    The efficacy of killing by bactericidal antibiotics has been reported to depend in large part on the ATP levels, with low levels of ATP leading to increased persistence after antibiotic challenge. Here, we show that an atp operon deletion strain of Salmonella enterica serovar Typhimurium lacking the ATP synthase was at least 10-fold more sensitive to killing by the fluoroquinolone antibiotic ciprofloxacin and yet showed either increased survival or no significant difference compared with the wild-type strain when challenged with aminoglycoside or β-lactam antibiotics, respectively. The increased cell killing and reduced bacterial survival (persistence) after fluoroquinolone challenge were found to involve metabolic compensation for the loss of the ATP synthase through central carbon metabolism reactions and increased NAD(P)H levels. We conclude that the intracellular ATP levels per se do not correlate with bactericidal antibiotic persistence to fluoroquinolone killing; rather, the central carbon metabolic pathways active at the time of challenge and the intracellular target of the antibiotic determine the efficacy of treatment.