YbdO Promotes the Pathogenicity of K1 by Regulating Capsule Synthesis.

K1 is the most popular neonatal meningitis-causing Gram-negative bacterium. As a key virulence determinant, the K1 capsule enhances the survival of K1 in human brain microvascular endothelial cells (HBMECs) upon crossing the blood-brain barrier; however, the regulatory mechanisms of capsule synthesis during K1 invasion of HBMECs remain unclear. Here, we identified YbdO as a transcriptional regulator that promotes K1 invasion of HBMECs by directly activating K1 capsule gene expression to increase K1 capsule synthesis. We found that deletion significantly reduced HBMEC invasion by K1 and meningitis occurrence in mice. Additionally, electrophoretic mobility shift assay and chromatin immunoprecipitation-quantitative polymerase chain reaction analysis indicated that YbdO directly activates and expression, which encode products involved in K1 capsule transport and synthesis by directly binding to the promoter. Furthermore, transcription was directly repressed by histone-like nucleoid structuring protein (H-NS), and we observed that acidic pH similar to that of early and late endosomes relieves this transcriptional repression. These findings demonstrated the regulatory mechanism of YbdO on K1 capsule synthesis, providing further insights into the evolution of K1 pathogenesis and host-pathogen interaction.