Bactericidal antibiotics kill pathogens and understanding the mechanisms of antibiotic lethality is important for combatting persistent infections. Both the growth rate and metabolic state of cells affect antibiotic lethality, but they are interrelated as growth affects metabolism and vice versa. Lopatkin et al. investigated the relative contribution of growth and metabolic state to antibiotic lethality by measuring growth rate and metabolism across a range of conditions (nine drugs of different classes, and diverse Gram-positive and Gram-negative bacteria) in which growth and metabolism were coupled and uncoupled (conditions in which only growth is nutrient-limited). The authors found that metabolic state and ATP levels at the time of treatment are more accurate predictors of lethality than growth rate, and determined a critical ATP threshold below which antibiotic lethality is negligible. These findings suggest that antibiotics will kill non-growing bacteria if metabolism is stimulated.
Lopatkin, A. J. et al. Bacterial metabolic state more accurately predicts antibiotic lethality than growth rate. Nat. Microbiol. https://doi.org/10.1038/s41564-019-0536-0 (2019)
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York, A. Metabolic state matters for antibiotic lethality. Nat Rev Microbiol 17, 646 (2019). https://doi.org/10.1038/s41579-019-0268-4