Defense Date

2011

Document Type

Thesis

Degree Name

Master of Science

Department

Microbiology & Immunology

First Advisor

Richard Marconi

Abstract

Borrelia hermsii, an etiologic agent of tick-borne relapsing fever, binds negative complement regulator factor H (FH) via its FhbA protein. Direct demonstration of the role of FhbA in the disease process has been hindered by the lack of genetic manipulation systems for the relapsing fever Borrelia. Here, we demonstrate successful generation of a B. hermsii strain YOR fhbA deletion mutant (Bh YORΔfhbA) that constitutively produces green fluorescent protein (GFP). Genetic manipulation did not affect growth rate or plasmid composition. Bh YORΔfhbA lost factor H-binding and C3b-inactivation capabilities, but retained resistance to killing in human serum and infectivity in mice. Stable production of GFP was demonstrated in vitro and in vivo. Collectively, these results suggest that B. hermsii employs an unidentified mechanism of complement evasion that is FH-independent and sufficient for persistence within the host. Additionally, this study represents a significant methodological advancement in the molecular characterization of relapsing fever spirochetes.

Rights

© The Author

Is Part Of

VCU University Archives

Is Part Of

VCU Theses and Dissertations

Date of Submission

6-22-2011

Share

COinS