a PCA plot showing divergence of transcriptional response to lung infection within the ear (9–47-Ear) and blood isolates (4559-Blood). rafR swap (9–47M) rewires pneumococcal transcriptional response only in the ear isolate background but not in the blood isolate. b Differential expression due to the rafR swap in the ear isolate background is spread throughout the pneumococcal genome. c Differential expression due to the rafR swap in the blood isolate background is limited to a genomic island. d–f Functional enrichment showed specific function being differentially expressed, including carbohydrate metabolism (d), ABC transporters (e), and sugar transporters (f). A: comparison of 9–47-Ear to 9–47M; B: 9–47-Ear to 4559-Blood; C: 9–47-Ear to 4559M; D: 9–47M to 4559-Blood; E: 9–47M to 4559M and F: 4559-Blood to 4559M. Asterisk (*) denotes statistically significant functional enrichment for the indicated strain–strain comparison.