Understanding microbial adaption within different natural environments remains a gap in knowledge in emerging infectious disease research. Tick-borne diseases continue to afflict human health, and given the vectors high reproductive potential, the ability to survive in extreme conditions, and the ability to transmit parasitic, virl, and bacterial pathogens, understanding pathogen colonization within the tick vector is particularly relevant to public health. One such pathogen is tick-borne relapsing fever (RF) spirochetes. The global distribution and economic burden of RF spirochetes on human health is underappreciated, especially considering the prevalence and impact of the disease on populations in impoverished countries, yet we do not understand how the pathogen adapts within the tick vector. A unique characteristic of the vector is that the ticks are extremely long-lived and can go years between feedings, yet the bacteria remain viable and transmissible. Additionally, the rapidity of feeding and subsequent transmission of the spirochetes differs significantly from other tick-borne diseases, further emphasizing the need to understand how RF spirochetes survive within the tick. One limitation that has prevented the development of disease preventing therapeutics has been a poor understanding of the molecular events contributing to RF spirochete colonization of the tick vector. To address this, we have established an in vivo system to study the complete tick-mammalian infectious cycle for Borrelia turicatae, a species of RF spirochete. We have identified a series of 20 consecutive plasmid localized genes that the spirochetes up- regulate during tick infection, and an in silico analysis indicated that the genes encode for putative outer membrane proteins (Omps). We have amplified, cloned, and expressed 15 of the genes in E. coli and propose to generate rabbit serum against the recombinant proteins, allowing us to determine if the proteins are surface exposed. Focusing on the confirmed Omps, we will determine the differential production of the Omps within two regions of the tick that B. turicatae must colonize to ensure the spirochetes continued life cycle, the midgut and salivary glands. At the completion of this proposal, we will better understand the surface proteome of B. turicatae during tick infection and we will determine if Omps are differentially produced within the midgut and salivary glands of the tick vector. Our findings will generate the data necessary for a competitive R01 application investigating if the Omps uniquely produced within the midgut and salivary glands are necessary for B. turicatae colonization of these tissues.

Public Health Relevance

Understanding how pathogenic microbes adapt within different natural environments remains a gap in knowledge in infectious disease research and is particularly relevant towards understanding a pathogen's maintenance and transmission. This proposal addresses a globally significant zoonotic disease and is focused on understanding how tick-borne relapsing fever spirochetes adapt within the vector. With estimates from the World Health Organization indicating that nearly half the world's population is at risk of acquiring a vector-borne disease, and given that arthropod vectors have high a reproductive potential and are able to survive in extreme conditions, understanding pathogen adaptation within the tick vector is particularly relevant toward public health.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Exploratory/Developmental Grants (R21)
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Vector Biology Study Section (VB)
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Breen, Joseph J
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Baylor College of Medicine
Schools of Medicine
United States
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Krishnavajhala, Aparna; Armstrong, Brittany A; Lopez, Job E (2018) Vector competence of geographical populations of Ornithodoros turicata for the tick-borne relapsing fever spirochete Borrelia turicatae. Appl Environ Microbiol :
Kim, H J; Filatov, S; Lopez, J E et al. (2017) Blood feeding of Ornithodoros turicata larvae using an artificial membrane system. Med Vet Entomol 31:230-233
Luo, Zhipu; Kelleher, Alan J; Darwiche, Rabih et al. (2017) Crystal Structure of Borrelia turicatae protein, BTA121, a differentially regulated  gene in the tick-mammalian transmission cycle of relapsing fever spirochetes. Sci Rep 7:15310
Krishnavajhala, Aparna; Wilder, Hannah K; Boyle, William K et al. (2017) Imaging of Borrelia turicatae Producing the Green Fluorescent Protein Reveals Persistent Colonization of the Ornithodoros turicata Midgut and Salivary Glands from Nymphal Acquisition through Transmission. Appl Environ Microbiol 83:
Wilder, Hannah K; Raffel, Sandra J; Barbour, Alan G et al. (2016) Transcriptional Profiling the 150 kb Linear Megaplasmid of Borrelia turicatae Suggests a Role in Vector Colonization and Initiating Mammalian Infection. PLoS One 11:e0147707
Lopez, Job E; Krishnavahjala, Aparna; Garcia, Melissa N et al. (2016) Tick-Borne Relapsing Fever Spirochetes in the Americas. Vet Sci 3:
Boyle, William K; Wilder, Hannah K; Lawrence, Amanda M et al. (2014) Transmission dynamics of Borrelia turicatae from the arthropod vector. PLoS Negl Trop Dis 8:e2767
Lopez, Job E; Wilder, Hannah K; Hargrove, Reid et al. (2013) Development of genetic system to inactivate a Borrelia turicatae surface protein selectively produced within the salivary glands of the arthropod vector. PLoS Negl Trop Dis 7:e2514