Together, these data demonstrate that in strain D39 (serotype 2), SpxR and CpsR work together through the 37-CE to repress capsule expression during pneumonia and lung-to-blood transition (Fig 4C–4E), whereas during sepsis—where we expect cps transcription to increase [32]—SpxR and CpsR derepress capsule expression, as evidenced by the 37-CE not being required in this environment (Δ37-CE strain: Fig 4F–4H). This evidence concerns the gene CAD and pneumonia.