A new role for host annexin A2 in establishing bacterial adhesion to vascular endothelial cells: lines of evidence from atomic force microscopy and an in vivo study

Xi He, Weiwei Zhang, Qing Chang, Zhengchen Su, Dejun Gong, Yixuan Zhou, Jie Xiao, Aleksandra Drelich, Yakun Liu, Vsevolod Popov, Xin Zhao, Maki Wakamiya, Angelo Gaitas, Fangling Lu, Bin Gong

Research output: Contribution to journalArticle

Abstract

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 bacterium 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 is lacking in the field of bacterial infections of ECs. 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. 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. We conclude that the endothelial surface ANXA2 plays an important role in initiating pathogen–host interactions, ultimately leading to bacterial anchoring on the vascular luminal surface.

Original languageEnglish (US)
JournalLaboratory Investigation
DOIs
StatePublished - Jan 1 2019

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Annexin A2
Bacterial Adhesion
Atomic Force Microscopy
Endothelial Cells
Cell Line
Rickettsia
Bacterial Infections
Blood Vessels
Staphylococcus aureus
Bacteria
Annexins
Antibodies
Epithelial Cells
Ligands

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Cell Biology

Cite this

A new role for host annexin A2 in establishing bacterial adhesion to vascular endothelial cells : lines of evidence from atomic force microscopy and an in vivo study. / He, Xi; Zhang, Weiwei; Chang, Qing; Su, Zhengchen; Gong, Dejun; Zhou, Yixuan; Xiao, Jie; Drelich, Aleksandra; Liu, Yakun; Popov, Vsevolod; Zhao, Xin; Wakamiya, Maki; Gaitas, Angelo; Lu, Fangling; Gong, Bin.

In: Laboratory Investigation, 01.01.2019.

Research output: Contribution to journalArticle

He, Xi ; Zhang, Weiwei ; Chang, Qing ; Su, Zhengchen ; Gong, Dejun ; Zhou, Yixuan ; Xiao, Jie ; Drelich, Aleksandra ; Liu, Yakun ; Popov, Vsevolod ; Zhao, Xin ; Wakamiya, Maki ; Gaitas, Angelo ; Lu, Fangling ; Gong, Bin. / A new role for host annexin A2 in establishing bacterial adhesion to vascular endothelial cells : lines of evidence from atomic force microscopy and an in vivo study. In: Laboratory Investigation. 2019.
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AU - Gong, Dejun

AU - Zhou, Yixuan

AU - Xiao, Jie

AU - Drelich, Aleksandra

AU - Liu, Yakun

AU - Popov, Vsevolod

AU - Zhao, Xin

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AU - Gaitas, Angelo

AU - Lu, Fangling

AU - Gong, Bin

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