Pseudomonas aeruginosa transcriptome adaptations from colonization to biofilm infection of skin wounds

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 biofilm wound infection may provide strategies for infection control. Toward this goal, we seeded log-phase P. aeruginosa (PAO1) into 3-day-old, full-thickness excision wounds (rabbit ear) and harvested the bacteria during colonization (Hrs 2 and 6), acute infection (Hr 24), and biofilm infection (Days 5 and 9) for transcriptome analysis (RNA-Seq). After 2-6 h in the wound, genes for metabolism and cell replication were down-regulated while wound-adaptation genes were up-regulated (vs. expression in log-phase culture). As the infection progressed from acute to biofilm infection, more genes became up-regulated than down-regulated, but the down-regulated genes enriched in more pathways, likely because the genes and pathways that bacteria already colonizing wounds up-regulate to establish biofilm infection are less known. Across the stages of infection, carbon-utilization pathways shifted. During acute infection, itaconate produced by myeloid cells appears to have been a carbon source because myeloid cell infiltration and the expression of the host gene, ACOD1, for itaconate production peaked coincidently with the expression of the PAO1 genes for itaconate transport and catabolism. Additionally, branched-chain amino acids are suggested to be a carbon source in acute infection and in biofilm infection. In biofilm infection, fatty acid degradation was also up-regulated. These carbon sources feed into the glyoxylate cycle that was coincidently up-regulated, suggesting it provided the precursors for P. aeruginosa to synthesize macromolecules in establishing wound infection.

Automated summary

In burn patients, Pseudomonas aeruginosa infection is a major cause of morbidity, and analyzing the pathogen's gene expression during wound infection transitions may provide strategies for infection control. Different carbon sources are utilized by P. aeruginosa at different stages of infection, with the glyoxylate cycle being up-regulated to provide precursors for synthesizing macromolecules in establishing wound infections.