Figure 1.
Epistasis between antibiotic resistance mutations and conjugative plasmids.
(A) Epistasis between mutations in genes gyrA, rpoB and rpsL and conjugative resistance plasmids (positive epistasis in grey, negative in black and no epistasis in white). Sign epistasis is indicated with “++”. (B) Distribution of the epistasis values. Median is positive (0.037) with bootstrap 95% confidence interval [0.021; 0.065], showing an overall level of positive epistasis between chromosomal resistance mutations and conjugative resistance plasmids. According to a Shapiro-Wilk W-test, the ε values do not follow a normal distribution (p = 0.000968).
Figure 2.
Mutation effect on the mean epistatic value.
(A) Mean epistatic value for each mutation. Error bars indicate twice the standard error. Note how the mean epistatic effect significantly differ between mutations (Kruskal-Wallis p = 0.0016) (B) Mutations become increasingly epistatic as their severity increases. Note how the mean absolute epistatic effect correlates with the fitness cost associated with each mutation (Spearman p = 0.006).
Figure 3.
Plasmid effect on the mean epistatic value.
(A) Mean epistatic value for each plasmid. Error bars indicate twice the standard error. Note how the mean epistatic effect does not significantly differ between plasmids (Kruskal-Wallis p = 0.6758). (B) Evidence for the lack of correlation between the fitness cost associated with each plasmid and its mean epistatic value (Spearman p = 0.188).
Figure 4.
Sign epistasis between chromosomal mutations and conjugative plasmids.
Sign epistasis occurs when the fitness of the strain carrying both resistance determinants (black bars) is greater than the fitness of at least one of the strains carrying a single resistance determinant (mutation – grey bars; or plasmid – white bars). The genotype D87G(R16) presents reciprocal sign epistasis [41]. Error bars represent twice the standard error.
Figure 5.
Evidence for epistasis between conjugative plasmids.
(A) Distribution of the types of epistatic interaction found between conjugative plasmids (positive epistasis in grey, negative epistasis in black and no epistasis in white). “Inc” indicates a combination of incompatible plasmids. The single case of sign epistasis is marked with ‘++’. (B) Distribution of the epistasis level, ε, whose median is −0.00083 with bootstrap confidence interval [−0.035; 0.061], showing that there are several cases of strong positive and negative epistasis despite the near 0 median.