The Factor H-Binding Site of CspZ as a Protective Target against Multistrain, Tick-Transmitted Lyme Disease

Author:

Marcinkiewicz Ashley L.1,Lieknina Ilva2,Yang Xiuli3,Lederman Patricia L.1,Hart Thomas M.14,Yates Jennifer1,Chen Wen-Hsiang56,Bottazzi Maria Elena567,Mantis Nicholas J.18ORCID,Kraiczy Peter9,Pal Utpal3,Tars Kaspars2,Lin Yi-Pin18ORCID

Affiliation:

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

2. Latvian Biomedical Research and Study Centre, Riga, Latvia

3. Department of Veterinary Medicine, Virginia-Maryland Regional College of Veterinary Medicine, University of Maryland, College Park, Maryland, USA

4. Department of Biological Sciences, State University of New York at Albany, Albany, New York, USA

5. Department of Pediatrics, National School of Tropical Medicine, Baylor College of Medicine, Houston, Texas, USA

6. Texas Children’s Hospital Center for Vaccine Development, Houston, Texas, USA

7. Department of Biology, Baylor University, Waco, Texas, USA

8. Department of Biomedical Sciences, State University of New York at Albany, Albany, New York, USA

9. Institute of Medical Microbiology and Infection Control, University Hospital of Frankfurt, Frankfurt, Germany

Abstract

The spirochete Borrelia burgdorferi sensu lato is the causative agent of Lyme disease (LD). The spirochetes produce the CspZ protein that binds to a complement regulator, factor H (FH). Such binding downregulates activation of host complement to facilitate spirochete evasion of complement killing. However, vaccination with CspZ does not protect against LD infection. In this study, we demonstrated that immunization with CspZ-YA, a CspZ mutant protein with no FH-binding activity, protected mice from infection by several spirochete genotypes introduced via tick feeding.

Funder

LOEWE Center DRUID

HHS | NIH | National Institute of Allergy and Infectious Diseases

National Science Foundation

U.S. Department of Defense

New York State Department of Health - Wadsworth Center

Publisher

American Society for Microbiology

Subject

Infectious Diseases,Immunology,Microbiology,Parasitology

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