Biosynthetic requirements of <i>P. aeruginosa</i> during wound infection.

<p>(A) <i>P. aeruginosa</i> must biosynthesize several amino acids, cofactors, and metabolic endproducts during growth <i>in vivo</i>. If mutants in >33% of genes predicted to be in the biosynthetic pathway of a given metabolite were more fit in both burn and chronic wounds than in MOPS-Succ (fold change ≥2, P<0.05, negative binomial test), that metabolite was said to be “Available” to <i>P. aeruginosa in vivo</i>. If 5–33% of genes predicted to be in the biosynthetic pathway of a given metabolite were more fit in both burn and chronic wounds than in MOPS-Succ, or if only one infection matched the criteria for “Available” as described above, that metabolite was said to be “Potentially Available”. If <5% of genes predicted to be in the biosynthetic pathway of a given metabolite were more fit in both burn and chronic wounds than in MOPS-Succ, that metabolite was said to be “Not Available”. Genes predicted to be involved in synthesis of necessary metabolites were identified from the PseudoCyc database (see <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004518#pgen.1004518.s010" target="_blank">Table S7</a> for details). (B) Kaplan-Meier survival curves of burned mice infected with PAO1 Δ<i>pabC</i>, PAO1 Δ<i>purF</i>, PAO1 Δ<i>hisE</i>, or PAO1 Δ<i>ilvD</i>. The first two strains are auxotrophic for metabolites predicted to be not available, and the last two strains are auxotrophic for metabolites predicted to be available. The experiment was performed with five mice per group, and the percent survival of all mice is shown (*, P<0.05, log-rank (Mantel-Cox) test).