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Fig 1.

Graphical depiction of the phenomenological definitions of susceptible, resistant, tolerant, and persistent (i.e., extreme tolerance).

A hypothetical time course antibiotic kill experiment is displayed graphically. A bactericidal antibiotic (e.g., a β-lactam) is added at 0 hours followed by measurements of cell viability over time. A fully susceptible population is rapidly killed (dashed, green-colored line), while a resistant population continues to grow in the presence of the antibiotic (red-colored line). Susceptible, L-form tolerant cells continue to actively replicate (dashed, blue-colored line); albeit at a reduced rate compared to resistant cells. In contrast, a susceptible, tolerant spheroplast population (blue-colored line) does not replicate and is ultimately killed but displays prolonged viability compared to susceptible cells. Finally, in the setting of extreme tolerance (so-called “persistence”), the majority of the population is rapidly killed, but a small subpopulation remains viable for an extended period (orange-colored line).

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