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Updated: Feb 7, 2026
Phage-Mediated Genetic Manipulation of the Lyme Disease Spirochete Borrelia burgdorferi
Published on: September 28, 2022
Crystal structure of the membrane attack complex assembly inhibitor BGA71 from the Lyme disease agent Borrelia
Kalvis Brangulis1,2, Inara Akopjana3, Ivars Petrovskis3
1Latvian Biomedical Research and Study Centre, Ratsupites 1 k-1, LV-1067, Riga, Latvia. kalvis@biomed.lu.lv.
Abstract:
Borrelia (B.) bavariensis, B. burgdorferi, B. afzelii, B. garinii, B. spielmanii, and B. mayonii are the causative agents in Lyme disease. Lyme disease spirochetes reside in infected Ixodes ticks and are transferred to mammalian hosts during tick feeding. Once transmitted, spirochetes must overcome the first line of defense of the innate immune system either by binding complement regulators or by terminating the formation of the membrane attack complex (MAC). In B. bavariensis, the proteins BGA66 and BGA71 inhibit complement activation by interacting with the late complement components C7, C8, and C9, as well as with the formed MAC. In this study, we have determined the crystal structure of the potent MAC inhibitor BGA71 at 2.9 Ǻ resolution. The structure revealed a cysteine cross-linked homodimer. Based on the crystal structure of BGA71 and the structure-based sequence alignment with CspA from B. burgdorferi, we have proposed a potential binding site for C7 and C9, both of which are constituents of the formed MAC. Our results shed light on the molecular mechanism of immune evasion developed by the human pathogenic Borrelia species to overcome innate immunity. These results will aid in the understanding of Lyme disease pathogenesis and pave the way for the development of new strategies to prevent Lyme disease.
Insights
Borrelia bavariensis uses BGA71 protein to inhibit the host immune system
Area of Science:
- Microbiology
- Immunology
- Structural Biology
Background:
- Lyme disease is caused by Borrelia species transmitted through Ixodes ticks.
- Borrelia spirochetes evade the innate immune system, including the complement system.
- The membrane attack complex (MAC) is a key component of complement-mediated immunity.
Purpose of the Study:
- To determine the crystal structure of Borrelia bavariensis protein BGA71.
- To elucidate the molecular mechanism by which BGA71 inhibits MAC formation.
- To understand Borrelia immune evasion strategies against human hosts.
Main Methods:
- X-ray crystallography was used to determine the structure of BGA71.
- Structure-based sequence alignment was performed with CspA from Borrelia burgdorferi.
- Potential binding sites for complement components C7 and C9 were proposed.
Main Results:
- The crystal structure of BGA71 was determined at 2.9 Å resolution.
- BGA71 forms a cysteine cross-linked homodimer.
- A potential binding site for MAC components C7 and C9 was identified.
Conclusions:
- BGA71 is a potent inhibitor of the membrane attack complex.
- The structure of BGA71 provides insights into Borrelia's immune evasion mechanisms.
- Understanding these mechanisms can inform new Lyme disease prevention strategies.
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