CsiR-Mediated Signal Transduction Pathway in Response to Low Iron Conditions Promotes Escherichia coli K1 Invasion and Penetration of the Blood-Brain Barrier

Author:

Zheng Yangyang123ORCID,Sun Hao12ORCID,Wang Yanling12,Jin Chen12,Li Xiaoya12,Pang Yu12,Ge Qianwen12,Wang Lei12,Liu Bin124

Affiliation:

1. National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, TEDA Institute of Biological Sciences and Biotechnology, Nankai University , Tianjin , People's Republic of China

2. Key Laboratory of Molecular Microbiology and Technology, Ministry of Education , Tianjin , People's Republic of China

3. Department of Microbiology, College of Life Sciences, Nankai University , Tianjin , People's Republic of China

4. Nankai International Advanced Research Institute , Shenzhen , People's Republic of China

Abstract

Abstract Escherichia coli K1 is the leading cause of neonatal gram-negative bacterial meningitis, but the pathogenesis of E coli K1 meningitis remains unclear. Blood-brain barrier (BBB) penetration is a crucial step in E coli meningitis development. Here, we uncovered the crucial role of CsiR, a GntR family regulator, in E coli K1 virulence. During infection, csiR expression was induced due to the derepression by Fur in the blood and human brain microvascular endothelial cells (HBMECs). CsiR positively regulated ilvB expression, which is associated with branched chain amino acid synthesis. Furthermore, we revealed that IlvB activated the FAK/PI3K pathway of HBMECs to induce actin cytoskeleton rearrangements, thereby promoting the bacterial invasion and penetration of the BBB. Overall, this study reveals a CsiR-mediated virulence regulation pathway in E coli K1, which may provide a useful target for the prevention or therapy of E coli meningitis.

Funder

National Natural Science Foundation of China

Distinguished Young Scholars of Tianjin

Natural Science Foundation (Key Project) of Tianjin

Natural Science Foundation of Shenzhen

Publisher

Oxford University Press (OUP)

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