Bacterial persisters in long-term infection: Emergence and fitness in a complex host environment
Fig 2
High-persisters in the multi-trait landscape.
(A) Lop (grey circle) and Hip (blue diamonds were analyzed via principle component analysis with respect to their similarity with other infection-linked traits: growth rate (GR_LB), adhesion, and ciprofloxacin MIC (cip). 446 isolates with complete trait sets were included. Hip isolates do not consistently cluster with any one additional trait. Each symbol represents a P. aeruginosa isolate. The first Hip isolates from a lineage (FirstHip, yellow triangles) were highlighted as Hip variants with mitigated effects of other accumulating mutations within the lineage to improve cross-lineage comparison. In each case, FirstHip and the remaining Hip isolates shift to various degrees from ‘naïve’ towards ‘adapted’ levels given the particular Hip dataset. We illustrate this using data ellipse enclosing samples approximately within the first standard deviation (t distribution, 68% of the set) for isolate sets characterized as FirstHip (yellow ellipse), and the remaining Hips (blue ellipse). (B) We visualized the association between lineages that produced Hips versus resistant isolates and/or slow growing isolates (identified by the minimum growth rate of lineage isolates falling below 70% of the P. aeruginosa PAO1 growth rate based on a 45 minute generation time in LB in microtiter wells). Association between variables is illustrated by a mosaic plot (multi-way contingency table visualization) where color indicates significant deviation from the expected frequency of lineages in each cell under trait independence using Pearson’s chi-squared test. Presence of isolates with a given trait in a lineage is indicated by ‘Yes’, absence by ‘No’.