Rickettsia rickettsii is the causative agent of one of the most severe tick-borne diseases in the United States. The compounding factors of rickettsial pathogenicity and route of tick transmission (horizontal and vertical) influence the ecology and epidemiology of human rickettsioses. Our long term goal is to elucidate the molecular mechanisms that are central to rickettsial transmission by ticks. The bacterial-derived molecular determinants of rickettsial infection of vertebrate cells have been described using various in vitr models. Our research indicates that rickettsial infection of tick hosts also utilizes similar processes described for infection of vertebrate host cells. However, the role of rickettsial proteins in tick infection is unknown. Likewise, although the tick actively responds to the infecting rickettsiae, the central mechanisms orchestrating the tick-derived response are not known. Thus, the experimental focus of this application emphasizes the roles of pathogenic determinants underlying rickettsial infection and the bacterial-induced alterations of the tick immune response mediating successful rickettsial colonization of the vector. The following specific aims will provide a better understanding of the constituents of rickettsial infection and transmission in arthropod vectors. 1) Defining the contribution of conserved surface cell antigens (Sca) to SFG Rickettsia infection of the tick vector. Sca proteins are known to be essential to rickettsial infection and dissemination in vertebrate cells. We hypothesize that there will be a distinct profile associated with infection of the arthropod vector. The objective of this aim is to define the role for rickettsial proteins during the infection process in the tick host. 2 To determine how the tick immune response to SFG Rickettsia correlates to vector competence. A vigorous tick response to SFG Rickettsia supports a species-specific host response to rickettsial infection. Therefore we hypothesize that a central molecule, Relish, is responsible for the balance between successful rickettsial colonization and clearance from the arthropod host. The objective of this aim is to delineate the IMD immune signaling system focusing on the production of active Relish in the tick host.

Public Health Relevance

Despite the overlapping distribution of ticks with multiple Rickettsia species, in nature, individual tick species are not infected with a diverse range of rickettsial species. We will examine the specificity of tick/Rickettsia relationships and delineate the molecular mechanisms of tick vector competence for spotted fever group Rickettsia to better understand the ecology and epidemiology of tick-borne rickettsial diseases.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI077784-09
Application #
9419168
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Perdue, Samuel S
Project Start
2009-08-20
Project End
2020-01-31
Budget Start
2018-02-01
Budget End
2019-01-31
Support Year
9
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Louisiana State University A&M Col Baton Rouge
Department
Pathology
Type
Schools of Veterinary Medicine
DUNS #
075050765
City
Baton Rouge
State
LA
Country
United States
Zip Code
70803
Sonenshine, Daniel E; Macaluso, Kevin R (2017) Microbial Invasion vs. Tick Immune Regulation. Front Cell Infect Microbiol 7:390
Harris, Emma K; Verhoeve, Victoria I; Banajee, Kaikhushroo H et al. (2017) Comparative vertical transmission of Rickettsia by Dermacentor variabilis and Amblyomma maculatum. Ticks Tick Borne Dis 8:598-604
Banajee, K H; Verhoeve, V I; Harris, E K et al. (2016) Effect of Amblyomma maculatum (Acari: Ixodidae) Saliva on the Acute Cutaneous Immune Response to Rickettsia parkeri Infection in a Murine Model. J Med Entomol 53:1252-1260
Banajee, Kaikhushroo H; Embers, Monica E; Langohr, Ingeborg M et al. (2015) Correction: Amblyomma maculatum Feeding Augments Rickettsia parkeri Infection in a Rhesus Macaque Model: A Pilot Study. PLoS One 10:e0137598
Pornwiroon, Walairat; Bourchookarn, Apichai; Paddock, Christopher D et al. (2015) Immunoproteomic profiling of Rickettsia parkeri and Rickettsia amblyommii. Ticks Tick Borne Dis 6:829-35
Banajee, Kaikhushroo H; Embers, Monica E; Langohr, Ingeborg M et al. (2015) Amblyomma maculatum Feeding Augments Rickettsia parkeri Infection in a Rhesus Macaque Model: A Pilot Study. PLoS One 10:e0135175
Petchampai, Natthida; Sunyakumthorn, Piyanate; Banajee, Kaikhushroo H et al. (2015) Identification of host proteins involved in rickettsial invasion of tick cells. Infect Immun 83:1048-55
Brown, Lisa D; Christofferson, Rebecca C; Banajee, Kaikhushroo H et al. (2015) Cofeeding intra- and interspecific transmission of an emerging insect-borne rickettsial pathogen. Mol Ecol 24:5475-89
Riley, Sean P; Macaluso, Kevin R; Martinez, Juan J (2015) Electrotransformation and Clonal Isolation of Rickettsia Species. Curr Protoc Microbiol 39:3A.6.1-20
Petchampai, Natthida; Sunyakumthorn, Piyanate; Guillotte, Mark L et al. (2014) Novel identification of Dermacentor variabilis Arp2/3 complex and its role in rickettsial infection of the arthropod vector. PLoS One 9:e93768

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