Fitness Landscape of Antibiotic Tolerance in Pseudomonas aeruginosa Biofilms
Figure 2
Gene- and pathway-level analysis of fitness profiles.
Comparative analysis of genome-wide footprinting data suggests that transposon insertions in or near 586 genes (see Dataset S3 for a complete list of these genes) cause reproducible, condition-dependent behavior that increases fitness in at least one setting (see Protocol S1). (A) The 586 genes (rows) were arranged using K-means clustering into six clusters shown on the left (C1 through C6). The hybridization scores shown for each gene were mean-centered and normalized to a standard deviation of one. This commonly used normalization puts each gene's fitness profile on a similar scale and facilitates comparison between the different conditions. Yellow indicates those conditions where mutants with transposons in or near the indicated gene underwent the greatest increases in abundance. Blue indicates conditions where transposons in or near the same gene were either deleterious or were slightly beneficial and resulted in a comparatively small increase in abundance. Column labels indicate the experimental condition: Bio-ND and Bio-TOB refer to transposon insertion libraries grown as biofilms and treated with no drug or tobramycin, respectively, and Pla-ND and Pla-TOB refer to libraries grown planktonically without or with tobramycin. Two biological replicates were performed in each condition and numbers indicate the repetition number. Gene names and annotations are in Dataset S3. (B) iPAGE was used to look for enrichment and depletion of functional categories (rows) among clusters C1 through C6 plus the set of genes not in any cluster (columns). Red (green) indicates that genes in the cluster were enriched (depleted) for the indicated category.