Figure 2.

Lytic interactions among 20 antibiotics against M. tuberculosis. (a) OD600 readings at the top concentrations for 20 individual drugs are shown. The cells have an OD600 of 0.14 in Day 0 (magenta line) and untreated cells grow to an OD600 of 0.54 by day 5 (top black line). At the highest concentration of some drugs, the OD600 drops below 0.14 and can be as low as 0.1, OD of media with no cells (bottom black line). For example, cys, eta, inh, lin and pre each reduce the cell population below the magenta line. We used OD = 0.14 as initial cell number, OD = 0.1 as no cells, and OD = 0.12 as the phenotype where 50% of the cells are lysed. The concentration of a drug that results in 50% lysis is defined as LC50 (50% lytic concentration). (b) Pairwise lytic interaction examples. We used the same methodology to measure static λ scores to measure lytic λ scores, after two modifications: we used LC50 for score calculation; when 50% lysis was not observed in neither singles nor the combination, we were unable to calculate a lytic λ score. In each subplot, single drugs are shown with white and orange lines, combination is shown with a two-color line. bdq + clz and pre + van was previously shown to have static synergy. These pairs also have lytic synergy since each pair has a lytic effect while neither of the singles do. Static and lytic synergy do not always co-occur. For example, pro + van does not have static synergy, however it has lytic synergy. fus + sq1 has static synergy but has no lytic synergy. (c) Heatmap of lytic interaction scores among 20 antibiotics. Blue, white or red indicate synergy, additivity or antagonism, respectively. Black squares are pairs for which lytic λ was not calculable. Among 190 pairs considered, only 9 were found to have lytic synergy (lytic λ < −0.5). (d) The effect of combination order on the distribution of lytic interaction scores. Description and interpretation are identical to Fig. 1d.