A Novel Laminin-Binding Protein Mediates Microbial-Endothelial Cell Interactions and Facilitates Dissemination of Lyme Disease Pathogens

Author:

Bista Sandhya1,Singh Preeti1,Bernard Quentin1,Yang Xiuli1,Hart Thomas23,Lin Yi-Pin24,Kitsou Chrysoula1,Singh Rana Vipin1,Zhang Fuming5,Linhardt Robert J567,Zhnag Kai8,Akins Darrin R9,Hritzo Lucy10,Kim Yuri10,Grab Dennis J10,Dumler J Stephen10,Pal Utpal111

Affiliation:

1. Department of Veterinary Medicine, University of Maryland, College Park, Maryland, USA

2. Department of Biological Science, State University of New York at Albany, Albany, New York, USA

3. Division of Infectious Diseases, Wadsworth Center New York State Department of Health, Albany, New York, USA

4. Department of Biomedical Science, State University of New York at Albany, Albany, New York, USA

5. Department of Chemical and Biological Engineering, Rensselaer Polytechnic Institute, Troy, New York, USA

6. Department of Chemistry and Chemical Biology, Rensselaer Polytechnic Institute, Troy, New York, USA

7. Department of Biology and Biomedical Engineering, Rensselaer Polytechnic Institute, Troy, New York, USA

8. Oral and Craniofacial Molecular Biology, School of Dentistry, Virginia Commonwealth University, Richmond, Virginia, USA

9. Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA

10. Department of Pathology, Uniformed Services University of the Health Sciences, Bethesda, Maryland

11. Virginia-Maryland College of Veterinary Medicine, College Park, Maryland

Abstract

Abstract Borrelia burgdorferi conserved gene products BB0406 and BB0405, members of a common B. burgdorferi paralogous gene family, share 59% similarity. Although both gene products can function as potential porins, only BB0405 is essential for infection. Here we show that, despite sequence homology and coexpression from the same operon, both proteins differ in their membrane localization attributes, antibody accessibility, and immunogenicity in mice. BB0406 is required for spirochete survival in mammalian hosts, particularly for the disseminated infection in distant organs. We identified that BB0406 interacts with laminin, one of the major constituents of the vascular basement membrane, and facilitates spirochete transmigration across host endothelial cell barriers. A better understanding of how B. burgdorferi transmigrates through dermal and tissue vascular barriers and establishes disseminated infections will contribute to the development of novel therapeutics to combat early infection.

Funder

National Institute of Allergy and Infectious Diseases

National Science Foundation

Global Lyme Alliance

Publisher

Oxford University Press (OUP)

Subject

Infectious Diseases,Immunology and Allergy

Reference42 articles.

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