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A New Role for Host Annexin A2 in Establishing Bacterial Adhesion to Vascular Endothelial Cell: Lines of Evidence from in vivo Study and Micro Force Spectroscopy

35 Pages Posted: 17 Mar 2019

See all articles by Xi He

Xi He

University of Texas Medical Branch-Galveston - Department of Pathology

Weiwei Zhang

Government of the People's Republic of China - Department of Cardiovascular Surgery

Qing Chang

University of Texas Medical Branch-Galveston - Department of Pathology

Zhengchen Su

University of Texas Medical Branch-Galveston - Department of Pathology

Dejun Gong

Government of the People's Republic of China - Department of Cardiovascular Surgery

Yixuan Zhou

Government of the People's Republic of China - Department of Cardiovascular Surgery

Jie Xiao

University of Texas Medical Branch-Galveston - Department of Pathology

Aleksandra Drelich

University of Texas Medical Branch-Galveston - Department of Pathology

Yakun Liu

University of Texas Medical Branch-Galveston - Department of Pathology

Vsevolod Popov

University of Texas Medical Branch-Galveston - Department of Pathology

Xin Zhao

McGill University

Maki Wakamiya

University of Texas Medical Branch-Galveston

Angelo Gaitas

Mount Sinai Health System - Icahn School of Medicine

Fanglin Lu

Government of the People's Republic of China - Department of Cardiovascular Surgery

Bin Gong

University of Texas Medical Branch-Galveston - Department of Pathology

More...

Abstract

Background: Understanding bacterial adhesion is challenging and critical to our understanding of the initial stages of the pathogenesis of endovascular bacterial infections. The vascular endothelial cell (EC) is the main target of Rickettsia, an obligately intracellular bacteria that causes serious systemic disease in humans and animals. But the mechanism(s) underlying bacterial adherence to ECs under shear stress from flowing blood prior to activation are unknown for any bacteria. Although host surface annexin a2 (ANXA2) has been identified to participate in efficient bacterial invasion of epithelial cells, direct evidence are completely lacking in the field of bacterial infections of ECs.

Methods: In the present study, we employ a novel, anatomically-based, in vivo quantitative bacterial-adhesion-to-vascular-EC system, combined with atomic force microscopy (AFM), to examine the role of endothelial luminal surface ANXA2 during rickettsial adherence to ECs. We also examined whether ANXA2 antibody affected binding of Staphylococcus aureus to ECs.

Findings: We found that deletion of ANXA2 impeded rickettsial attachment to the ECs in vitro and blocked rickettsial adherence to the blood vessel luminal surface in vivo. The AFM studies established that EC surface ANXA2 acts as an adherence receptor for rickettsiae, and that rickettsial adhesin OmpB is the associated bacterial ligand. Furthermore, pretreatment of ECs with anti-ANXA2 antibody reduced EC surface-associated S. aureus.

Interpretation: The endothelial surface ANXA2 plays an important role in initiating pathogen-host interactions, ultimately leading to bacterial anchoring on the vascular luminal surface.

Funding: This work was supported by NIH (B.G.) and Natural Science Foundation of China (F.L.).

Declaration of Interest: The authors declare that they have no conflicts of interest.

Ethical Approval: All animal experiments were performed according to protocols approved by the Institutional Animal Care and Use Committee of the University of Texas Medical Branch (UTMB).

Keywords: bacterial adhesion, vascular endothelial cell, annexin A2, atomic force microscopy, rickettsial infection, Staphylococcus aureus

Suggested Citation

He, Xi and Zhang, Weiwei and Chang, Qing and Su, Zhengchen and Gong, Dejun and Zhou, Yixuan and Xiao, Jie and Drelich, Aleksandra and Liu, Yakun and Popov, Vsevolod and Zhao, Xin and Wakamiya, Maki and Gaitas, Angelo and Lu, Fanglin and Gong, Bin, A New Role for Host Annexin A2 in Establishing Bacterial Adhesion to Vascular Endothelial Cell: Lines of Evidence from in vivo Study and Micro Force Spectroscopy (March 15, 2019). Available at SSRN: https://ssrn.com/abstract=3353360

Xi He

University of Texas Medical Branch-Galveston - Department of Pathology

Galveston, TX
United States

Weiwei Zhang

Government of the People's Republic of China - Department of Cardiovascular Surgery

Shanghai
China

Qing Chang

University of Texas Medical Branch-Galveston - Department of Pathology

Galveston, TX
United States

Zhengchen Su

University of Texas Medical Branch-Galveston - Department of Pathology

Galveston, TX
United States

Dejun Gong

Government of the People's Republic of China - Department of Cardiovascular Surgery

Shanghai
China

Yixuan Zhou

Government of the People's Republic of China - Department of Cardiovascular Surgery

Shanghai
China

Jie Xiao

University of Texas Medical Branch-Galveston - Department of Pathology

Galveston, TX
United States

Aleksandra Drelich

University of Texas Medical Branch-Galveston - Department of Pathology

Galveston, TX
United States

Yakun Liu

University of Texas Medical Branch-Galveston - Department of Pathology

Galveston, TX
United States

Vsevolod Popov

University of Texas Medical Branch-Galveston - Department of Pathology

Galveston, TX
United States

Xin Zhao

McGill University

1001 Sherbrooke St. W
Montreal, Quebec H3A 1G5
Canada

Maki Wakamiya

University of Texas Medical Branch-Galveston

Galveston, TX 77555
United States

Angelo Gaitas

Mount Sinai Health System - Icahn School of Medicine

One Gustave L. Levy Place
New York, NY 10029-6574
United States

Fanglin Lu (Contact Author)

Government of the People's Republic of China - Department of Cardiovascular Surgery ( email )

Shanghai
China

Bin Gong

University of Texas Medical Branch-Galveston - Department of Pathology ( email )

Galveston, TX
United States

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