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Published on: January 27, 2021
An ArcA-Modulated Small RNA in Pathogenic Escherichia coli K1
Hao Sun1,2,3,4, Yajun Song1,2,3,4, Fang Chen1,2,3
1TEDA Institute of Biological Sciences and Biotechnology, Nankai University, Tianjin, China.
Abstract:
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.
Insights
Escherichia coli K1 meningitis is a serious newborn threat. Researchers found that downregulating small RNA-17 helps E. coli K1 survive blood and invade the brain, offering new treatment targets.
Area of Science:
- Microbiology
- Molecular Biology
- Pathogenesis
Background:
- Escherichia coli K1 is a primary cause of neonatal meningitis.
- Understanding E. coli K1's adaptation mechanisms in host blood is crucial for developing treatments and preventing neurological damage.
Purpose of the Study:
- To investigate the molecular mechanisms E. coli K1 uses for survival and pathogenicity in host blood.
- To identify novel regulatory elements involved in E. coli K1's adaptation to the blood environment.
Main Methods:
- Identification and characterization of a novel small RNA, sRNA-17, in E. coli K1.
- Gene expression analysis, including transcriptome analysis, to understand sRNA-17 regulation and targets.
- Bacterial growth assays in blood and invasion assays using human brain microvascular endothelial cells.
Main Results:
- A novel small RNA, sRNA-17, was identified in E. coli K1.
- ArcA was found to downregulate sRNA-17 expression in microaerophilic blood.
- Deletion of sRNA-17 enhanced E. coli K1's growth in blood and its ability to invade brain endothelial cells.
- sRNA-17 was shown to regulate numerous differentially expressed genes.
Conclusions:
- ArcA-mediated downregulation of sRNA-17 benefits E. coli K1 survival in the bloodstream.
- This regulatory mechanism facilitates E. coli K1's penetration of the blood-brain barrier.
- The findings reveal a key signaling pathway for E. coli K1 host adaptation and meningitis pathogenesis.
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