Fig. 1: S. aureus adapts to the metabolic airway milieu.

A Phylogenetic tree illustrating within-host evolution of S. aureus during persistent pulmonary infection (cystic fibrosis, blue clade). This model assumes genetic bottlenecks upon transmission and expansion of a single lineage during infection. Only mutations acquired within the host (i.e., blue branches) are considered in the analysis. B Output of the convergence analysis: the size of the dots is proportional to the number of independent (i.e., acquired de novo within the host) protein-altering mutations in genes of the TCA cycle and surrounding pathways. The relative mutation rate is equivalent to a rate ratio in Poisson models and calculated as: (mutations in gene x/length of gene x)/(mutations in all genes/length of all genes). A rate <1 (gray shading) indicates less mutations than the mean across the genome, suggesting that the gene is conserved during infection. GLY glycolysis, GLN gluconeogenesis, PPP pentose phosphate pathway, TCA tricarboxylic acid/Krebs cycle, UREA urea cycle. C Gene maps with position, type, and evolutionary niche of the de novo mutations. D Relative levels of fumarate and itaconate in sputum from healthy subjects (HS) and patients with cystic fibrosis (CF). Each data point is the mean ± SEM; n = 5 (HS) and n = 9 (CF). Statistical significance was determined using the Mann–Whitney U test (**p = 0.0040, ***p = 0.0010).