Table_7_An ArcA-Modulated Small RNA in Pathogenic Escherichia coli K1.XLSX

Escherichia coli K1 is the leading cause of meningitis in newborns. Understanding the molecular basis of E. coli K1 pathogenicity will help develop treatment of meningitis and prevent neurological sequelae. E. coli K1 replicates in host blood and forms a high level of bacteremia to cause meningitis in human. However, the mechanisms that E. coli K1 employs to sense niche signals for survival in host blood are poorly understood. We identified one intergenic region in E. coli K1 genome that encodes a novel small RNA, sRNA-17. The expression of sRNA-17 was downregulated by ArcA in microaerophilic blood. The ΔsRNA-17 strain grew better in blood than did the wild-type strain and enhanced invasion frequency in human brain microvascular endothelial cells. Transcriptome analyses revealed that sRNA-17 regulates tens of differentially expressed genes. These data indicate that ArcA downregulates the sRNA-17 expression to benefit bacterial survival in blood and penetration of the blood–brain barrier. Our findings reveal a signaling mechanism in E. coli K1 for host adaptation.

大肠杆菌K1（Escherichia coli K1）是引发新生儿脑膜炎的首要致病菌。阐明大肠杆菌K1致病性的分子机制，将有助于开发脑膜炎治疗方案并预防神经系统后遗症。大肠杆菌K1可在宿主血液中增殖并形成高滴度菌血症，进而引发人类脑膜炎。然而，大肠杆菌K1感知宿主血液微环境信号以实现在血液中存活的具体机制，目前仍未明确。本研究在大肠杆菌K1基因组中鉴定到一段编码新型小RNA（small RNA，sRNA）的基因间区，将其命名为sRNA-17。在微需氧血液环境中，ArcA可下调sRNA-17的表达。与野生型菌株相比，sRNA-17基因缺失菌株在血液中的生长能力更强，且对人类脑微血管内皮细胞（human brain microvascular endothelial cells）的侵袭频率显著提升。转录组分析结果显示，sRNA-17可调控数十个差异表达基因。上述数据表明，ArcA通过下调sRNA-17的表达，助力细菌在血液中存活并穿透血脑屏障（blood–brain barrier）。本研究揭示了大肠杆菌K1中参与宿主适应性的信号调控机制。