Lyme borreliosis is a prevalent vector-borne disease in the United States, Europe, and parts of Asia, caused the infection with the bacterial pathogen Borrelia burgdorferi. Despite several decades of intense studies, many fundamental aspects of pathogen biology and infection remain largely unknown. B. burgdorferi infection can be difficult to diagnose, and a vaccine to prevent disease in humans is currently unavailable. The application will study how a select set of unique borrelial gene-products BB0323, BBA52 and BBA57 that play important roles in the spirochete infection cycle, contribute to specific aspects of microbial biology and pathogenesis and also assess their potential utility as Lyme disease vaccines. We have four major goals. First, we will examine how a critical virulence determinant of B. burgdorferi, BB0323 undergoes two-step proteolytic processing that ultimately produce distinct N- and C-terminal polypeptides, which play specific roles in cell fission and infectivity. Second, we have discovered that BBA52 is critical for pathogen transmission from ticks to mice and that the protein binds to a receptor in ticks. We propose to study a potential function of BBA52 in vector-pathogen interaction and its role in B. burgdorferi persistence and transmission through ticks. Third, we show that BBA57, a borrelial gene-product important for early spirochete infection in mice, is a major trigger of Lyme arthritis. Our studies will dissect detail molecular and cellular mechanisms of how BBA57 triggers host inflammatory responses and also facilitates spirochete infection. Finally, the proposed study will explore the identification f new vaccine candidates as well as New castle disease virus (NDV) vector-based immunization strategies against Lyme disease. As NDV appears to be safe in humans and is currently in use for therapeutic treatment of cancer patients, the proposed study will establish a foundation for it utility as a possible vaccine vector against human Lyme disease. In sum, these studies will contribute to the understanding of the intriguing biology and infectivity of B. burgdorferi and hel develop novel preventive and therapeutic measures to combat infection.

Public Health Relevance

Lyme disease is a prevalent infection caused by the tick-borne bacterial pathogen Borrelia burgdorferi. We propose to study how a select set of B. burgdorferi antigens that support pathogen persistence contributes to microbial biology, infection and pathogenesis. We also propose to identify novel vaccine targets as well immunization platforms that induce protective host immunity against B. burgdorferi infection.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project (R01)
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Host Interactions with Bacterial Pathogens Study Section (HIBP)
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Breen, Joseph J
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University of Maryland College Park
Veterinary Sciences
Schools of Earth Sciences/Natur
College Park
United States
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Koci, Juraj; Bernard, Quentin; Yang, Xiuli et al. (2018) Borrelia burgdorferi surface protein Lmp1 facilitates pathogen dissemination through ticks as studied by an artificial membrane feeding system. Sci Rep 8:1910
Zhuang, Xuran; Yang, Xiuli; Altieri, Amanda S et al. (2018) Borrelia burgdorferi surface-located Lmp1 protein processed into region-specific polypeptides that are critical for microbial persistence. Cell Microbiol 20:e12855
Kitsou, Chrysoula; Pal, Utpal (2018) Ixodes Immune Responses Against Lyme Disease Pathogens. Front Cell Infect Microbiol 8:176
Hart, Thomas; Yang, Xiuli; Pal, Utpal et al. (2018) Identification of Lyme borreliae proteins promoting vertebrate host blood-specific spirochete survival in Ixodes scapularis nymphs using artificial feeding chambers. Ticks Tick Borne Dis 9:1057-1063
Bernard, Quentin; Smith, Alexis A; Yang, Xiuli et al. (2018) Plasticity in early immune evasion strategies of a bacterial pathogen. Proc Natl Acad Sci U S A 115:E3788-E3797
Marcinkiewicz, Ashley L; Lieknina, Ilva; Kotelovica, Svetlana et al. (2018) Eliminating Factor H-Binding Activity of Borrelia burgdorferi CspZ Combined with Virus-Like Particle Conjugation Enhances Its Efficacy as a Lyme Disease Vaccine. Front Immunol 9:181
Marques, Adriana R; Yang, Xiuli; Smith, Alexis A et al. (2017) Citrate Anticoagulant Improves the Sensitivity of Borreliella (Borrelia) burgdorferi Plasma Culture. J Clin Microbiol 55:3297-3299
Zhang, Kai; Bian, Jiang; Deng, Yijie et al. (2016) Lyme disease spirochaete Borrelia burgdorferi does not require thiamin. Nat Microbiol 2:16213
Ye, Meiping; Sharma, Kavita; Thakur, Meghna et al. (2016) HtrA, a Temperature- and Stationary Phase-Activated Protease Involved in Maturation of a Key Microbial Virulence Determinant, Facilitates Borrelia burgdorferi Infection in Mammalian Hosts. Infect Immun 84:2372-2381
Yang, Xiuli; Lin, Yi-Pin; Heselpoth, Ryan D et al. (2016) Middle region of the Borrelia burgdorferi surface-located protein 1 (Lmp1) interacts with host chondroitin-6-sulfate and independently facilitates infection. Cell Microbiol 18:97-110

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