Fig 1.
Schematic illustration of the evolvability of antibiotic resistance under three scenarios.
A strain’s evolvability is defined operationally as the maximum increase in resistance from an initially susceptible genotype during one round of drug selection. (A) Null model, with no effect of genetic background on evolvability. (B) Diminishing-returns model, such that backgrounds with low initial resistance are more evolvable than backgrounds that are initially more resistant. (C) Idiosyncratic-effects model, in which evolvability varies among genetic backgrounds but is uncorrelated with their initial level of resistance. MIC, minimum inhibitory concentration.
Fig 2.
Intrinsic resistance usually declined over time in the absence of drug exposure.
Comparison of the LTEE ancestor and four independently derived clones sampled after 50,000 generations for their susceptibilities to ampicillin, ceftriaxone, ciprofloxacin, and tetracycline (A–D). MICs are shown on a log2-transformed scale to reflect the fact that antibiotic concentrations were tested across a series of 2-fold dilutions. In each panel, points show values obtained from 32 and 8 replicate assays for the ancestor and derived strains, respectively. Horizontal bars show the median of the log2-transformed MIC values for each strain on each antibiotic. The absolute values of the concentrations shown on the y-axis differ among the four antibiotics, but the range is the same in each panel. The underlying data for this figure may be found here: https://datadryad.org/stash/dataset/doi:10.5061/dryad.g41hg96. LTEE, long-term evolution experiment; MIC, minimum inhibitory concentration.
Table 1.
Statistical analyses of declines in intrinsic resistance during relaxed selection of clones sampled at generation 50,000 of the LTEE.
Fig 3.
Genetic background affects the evolvability of LTEE lines exposed to antibiotics.
Lines joining susceptible parental strains with their daughter mutants show the increases in resistance during one round of selection with ampicillin, ceftriaxone, ciprofloxacin, and tetracycline (A–D). If the slope of a derived strain is greater than that of the ancestor, then it has greater evolvability; and vice versa. Median MICs are shown on a log2-transformed scale to reflect the fact that antibiotic concentrations were tested across a series of 2-fold dilutions. The y-axis ranges for the four drugs have been scaled to the ceftriaxone environment, which had the largest gains in resistance between the susceptible parental cells and the resistant daughter cells. The underlying data for this figure may be found here: https://datadryad.org/stash/dataset/doi:10.5061/dryad.g41hg96. LTEE, long-term evolution experiment; MIC, minimum inhibitory concentration.
Table 2.
Statistical analyses of diminishing-returns trends in resistance evolvability of clones sampled at generation 50,000 of the LTEE.
Table 3.
Statistical analyses of idiosyncratic patterns in resistance evolvability of clones sampled at generation 50,000 of the LTEE.
Fig 4.
Capacity to evolve tetracycline resistance was diminished early in one LTEE lineage.
(A) Comparison of the intrinsic tetracycline resistance of the ancestor and a time series of derived strains isolated from the Ara+5 population. Strains are ordered by their time of isolation. The strain identifiers begin with a number corresponding to the generation (in thousands) of their isolation, followed by an arbitrary letter; strains 2A and 2B, for example, are two clones isolated at generation 2,000 of the LTEE. (B) Comparison of the evolved resistance levels after one round of drug selection, based on the MICs of the mutant daughter cells derived from the corresponding parental strains. MICs are shown on a log2-transformed scale to reflect the fact that the concentrations of antibiotics were tested across a series of 2-fold dilutions. (C) Evolvability is quantified for each strain as the difference in the log2-transformed MICs of the parental strain and its corresponding daughter mutant. Points show 10 independent replicates per strain. Horizontal bars show the median log2-transformed MICs (A, B) for 10 replicate assays and the evolvability (C) based on the corresponding 10 paired differences. The underlying data for this figure may be found here: https://datadryad.org/stash/dataset/doi:10.5061/dryad.g41hg96. LTEE, long-term evolution experiment; MIC, minimum inhibitory concentration.
Table 4.
Statistical analyses comparing tetracycline resistance evolvability of clones isolated from the Ara+5 population at different generations to the LTEE ancestor.