Fig 1.
Quantitative cross-resistance network.
Each node represents a phage strain, and arrows between nodes show directional CRF between two phages. The line widths are scaled by the proportion of replicate mutants selected against the focal phage (origin node) that have resistance above the binary threshold (S1 Fig) to the second phage (target node). Node colours define resistance modules identified using an ‘edge-betweenness’ algorithm. A subset of 20 phage strains that all showed strong symmetric cross-resistance were grouped together as the node labelled ‘Other’. CRF, cross-resistance frequency.
Fig 2.
Relationships of cross-resistance range with relative fitness and the strength of focal resistance.
Relationship between cross-resistance range (the proportion of nonfocal phages to which the bacterial mutant has resistance above the binary threshold) and relative fitness of spontaneous resistance mutants (A) measured as growth relative to the ancestral strain in phage-free standard media conditions (raw data provided in S2 Data) and (B) the strength of focal resistance, given as growth in the presence of the phage selected against, relative to growth in the absence of phage (RBG). RBG, relative bacterial growth.
Fig 3.
Genetic basis of phage resistance.
Circles represent different phage-resistant mutants selected against different focal phages (indicated by the colour shade; see key), and dots on each circle show the position of mutated genes. Colour represents the cross-resistance profile of each sequenced resistant mutant: resistance within module 1 (purple), within module 2 (green), and between modules (generalist resistance, blue).
Fig 4.
Relative fitness of resistant mutations grouped by cross-resistance type and mutational target.
Fitness relative to the phage-susceptible PAO1 ancestor of 263 spontaneous resistant mutants sorted by (A) cross-resistance type or (B) mutated locus. Colours denote cross-resistance type: within module 1 only (purple), within module 2 only (green), and between modules (blue). The dashed line (relative fitness = 1) represents equal fitness to the ancestor.
Fig 5.
Relative mutational frequency for resistance against phage pairs exerting symmetrical, asymmetrical, or no cross-resistance.
Relative mutational frequency compares the frequency of resistance mutations against phage pairs to the geometric mean of mutational frequency against each individual phage. Dashed line represents equal frequency of resistance mutations against a phage pair versus the constituent phages individually. Raw data are provided in S5 Data.