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Front Cell Infect Microbiol. 2019 Jan 9;8:448. doi: 10.3389/fcimb.2018.00448. eCollection 2018.

Transactivated Epidermal Growth Factor Receptor Recruitment of α-actinin-4 From F-actin Contributes to Invasion of Brain Microvascular Endothelial Cells by Meningitic Escherichia coli.

Fu J1,2, Li L1,2, Yang X1,2, Yang R1,2, Amjad N1,2, Liu L1,2, Tan C1,2,3,4, Chen H1,2,3,4, Wang X1,2,3,4.

Author information

1
State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.
2
Key Laboratory of Preventive Veterinary Medicine in Hubei Province, The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, China.
3
Key Laboratory of Development of Veterinary Diagnostic Products, Ministry of Agriculture of the People's Republic of China, Wuhan, China.
4
International Research Center for Animal Disease, Ministry of Science and Technology of the People's Republic of China, Wuhan, China.

Abstract

Bacterial penetration of the blood-brain barrier requires its successful invasion of brain microvascular endothelial cells (BMECs), and host actin cytoskeleton rearrangement in these cells is a key prerequisite for this process. We have reported previously that meningitic Escherichia coli can induce the activation of host's epidermal growth factor receptor (EGFR) to facilitate its invasion of BMECs. However, it is unknown how EGFR specifically functions during this invasion process. Here, we identified an important EGFR-interacting protein, α-actinin-4 (ACTN4), which is involved in maintaining and regulating the actin cytoskeleton. We observed that transactivated-EGFR competitively recruited ACTN4 from intracellular F-actin fibers to disrupt the cytoskeleton, thus facilitating bacterial invasion of BMECs. Strikingly, this mechanism operated not only for meningitic E. coli, but also for infections with Streptococcus suis, a Gram-positive meningitis-causing bacterial pathogen, thus revealing a common mechanism hijacked by these meningitic pathogens where EGFR competitively recruits ACTN4. Ever rising levels of antibiotic-resistant bacteria and the emergence of their extended-spectrum antimicrobial-resistant counterparts remind us that EGFR could act as an alternative non-antibiotic target to better prevent and control bacterial meningitis.

KEYWORDS:

bacterial meningitis; cytoskeleton; epidermal growth factor receptor; invasion; α-actinin-4

PMID:
30687645
PMCID:
PMC6333852
DOI:
10.3389/fcimb.2018.00448
[Indexed for MEDLINE]
Free PMC Article

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