Pseudomonas aeruginosa transcriptome adaptations from colonization to chronic infection of skin wounds. Pseudomonas aeruginosa PAO1

In burn patients Pseudomonas aeruginosa infection is a major cause of morbidity. Analysis of the pathogen's gene expression as it transitions from colonization to acute and then chronic wound infection may provide strategies for infection-control. Toward this goal, we seeded log-phase P. aeruginosa (PAO1) into three-day-old full-thickness excision wounds (rabbit ear) and harvested the bacteria at colonization (Hrs 2 and 6), acute infection (Hr 24), and chronic infection (Days 5 and 9) for transcriptome analysis (RNA-Seq). At Hrs 2-6, the COGs of log-phase-culture PAO1 related to metabolism and cell replication down-regulated while wound-adaptation COGs up-regulated. From acute to chronic infection, more genes up-regulated than down-regulated, but more down-regulated genes enriched in pathways, possibly because pathways bacteria already colonizing wounds up-regulate to establish chronic infection are less well annotated. Pathways involved in carbon utilization shifted across stages of infection. During acute infection, myeloid-cell-produced itaconate appears to have been a carbon source, suggested by the coincidence of peak myeloid cell wound infiltration, ACOD1 expression (for itaconate production), and PAO1 expression of itaconate-catabolism genes. Additionally, branched chain amino acids are a suggested carbon source in acute infection and in chronic infection when fatty acid degradation was additionally up-regulated. These carbon sources produce the end-product acetate that feeds into the up-regulated glyoxylate shunt to provide precursors P. aeruginosa needs to synthesize macromolecules in establishing wound infection.