Campylobacter jejuni extracellular vesicles harboring cytolethal distending toxin bind host cell glycans and induce cell cycle arrest in host cells

Author:

Le Lena Hoang My12,Elgamoudi Bassam3ORCID,Colon Nina1ORCID,Cramond Angus1,Poly Frederic4ORCID,Ying Le15ORCID,Korolik Victoria3ORCID,Ferrero Richard L.125ORCID

Affiliation:

1. Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, Victoria, Australia

2. Department of Microbiology, Biomedicine Discovery Institute, Monash University, Victoria, Australia

3. Institute for Glycomics, Griffith University, Gold Coast, Queensland, Australia

4. Enteric Diseases Department, Naval Medical Research Centre, Silver Springs, Maryland, USA

5. Department of Molecular and Translational Sciences, Monash University, Victoria, Australia

Abstract

Campylobacter jejuni is the leading cause of foodborne gastroenteritis in humans worldwide and a significant cause of childhood mortality due to diarrheal disease in developing countries. A major factor by which C. jejuni causes disease is a toxin, called cytolethal distending toxin (CDT). The biology of this toxin, however, is poorly understood. In this study, we report that C. jejuni CDT is protected within membrane blebs, known as extracellular vesicles (EVs), released by the bacterium. We showed that proteins on the surfaces of EVs are not required for EV uptake by host cells. Furthermore, we identified several sugar receptors that may be required for EV binding to host cells. By studying the EV-associated form of C. jejuni CDT, we will gain a greater understanding of how C. jejuni intoxicates host cells and how EV-associated CDT may be used in various therapeutic applications, including as anti-tumor therapies.

Funder

Department of Education and Training | Australian Research Council

DHAC | National Health and Medical Research Council

Griffith University

MU | Faculty of Medicine, Nursing and Health Sciences, Monash University

Department of Business and Innovation, Victoria State Government

Publisher

American Society for Microbiology

Subject

Infectious Diseases,Cell Biology,Microbiology (medical),Genetics,General Immunology and Microbiology,Ecology,Physiology

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