Source data of "Identification of a mechanical signaling pathway activating type 1 fimbriae via a ZraSR two-component system in neonatal meningitis-associated Escherichia coli"

Escherichia coli K1 (E. coli K1) meningitis develops after the bacteria cross the blood-brain barrier (BBB), however, the molecular mechanisms underlying this process remain incompletely understood. Adhesion to human brain microvascular endothelial cells (HBMECs), which constitute the BBB is considered important in E. coli K1 bacterial penetration into the central nervous system. Here, we report a complete signal regulatory pathway in which the ZraSR two-component system (TCS) senses mechanical stimuli induced by initial host cell attachment and directly activates the expression of type 1 fimbriae, specifically the FimH adhesin. This activation enhances E. coli K1 invasion into HBMECs. Disruption of this signaling pathway severely attenuates the progression of meningitis and reduces the production of proinflammatory factors triggered by E. coli K1 infection in vivo. These findings suggest that components of this pathway may serve as potential targets for novel therapeutic strategies against E. coli K1 infection.