Additional file 1: of When more is less: Emergent suppressive interactions in three-drug combinations

 Figure S1. Comparison of relative optical density measurement to growth rate measurement. Figure S2. Comparison of relative optical density measurement to colony forming units. Figure S3. Emergent three-way interaction measures in E. coli BW25113. Figure S4. Suppressive three-drug interactions in S. epidermidis 14990 and E. coli CFT073. Figure S5. Suppressor and suppressee antibiotics for S. epidermidis 14990 and E. coli CFT07. Table S1. Full data set for 14 drugs in E. coli BW25113, S. epidermidis 14990, and E. coli CFT073. Table S2. Emergent suppressive three-drug combinations from 14 antibiotics (see Methods, Fig. 1) for E. coli CFT073, E. coli BW25113, S. epidermidis 14990. (PDF 7668 kb

Supplementary Information from Uncovering emergent interactions in three-way combinations of stressors

Understanding how multiple stressors interact is needed to predict the dynamical outcomes of diverse biological systems, ranging from drug-resistant pathogens that are combated and treated with combination drug therapies to ecosystems impacted by environmental toxicants or disturbances. Nevertheless, extensive studies of higher-order (more than two component) interactions have been lacking. Here, we conduct experiments using 20 three-drug combinations and their effects on the bacterial growth of <i>Escherichia coli</i>. We report our measurements of growth rates in single, pairwise and triple-drug combinations. To uncover emergent interactions, we derive a simple framework to calculate expectations for three-way interactions based on the measured impact of each individual stressor and of each pairwise interaction. Using our framework, we find that (i) emergent antagonisms are more common than emergent synergies and (ii) emergent antagonisms are more common and emergent synergies are more rare than would be inferred from measures of net effects that do not disentangle pairwise interactions from three-way interactions