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. 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. Therefore, the broad hypothesis being tested is that unique tick-derived factors are required for successful horizontal and vertical transmission of spotted fever group (SFG) Rickettsia. Preliminary evidence indicates rickettsial transmission is dependent on the appropriate tick/Rickettsia relationship and the pathogenic nature of the Rickettsia. It is also known that ticks actively respond to the infecting rickettsiae;however, the extent to which modulation of tick-derived molecules is required for rickettsial survival within the tick is not known. Thus, the experimental focus of this proposal is to delineate the specificity of tick/Rickettsia relationships, the relationship between rickettsial pathogenicity and transmission, and to define the tick-derived molecules associated with rickettsial infection via comparative analysis of different tick and Rickettsia species. The previously undefined parameters of tick/Rickettsia interactions will be determined in the following specific aims. 1) Characterize the horizontal and vertical transmission of pathogenic and nonpathogenic SFG Rickettsia in tick hosts in vivo. The previously unknown kinetics of transmission for six species of SFG Rickettsia will be assessed in Amblyomma and Dermacentor ticks. Horizontal transmission of rickettsiae from Rickettsia-infected ticks to vertebrate hosts will be determined using a laboratory model of tick infestation. The efficiency of vertical transmission of Rickettsia will be assessed by fluorescence in situ hybridization and quantitative real-time PCR (qPCR) and the influence of SFG Rickettsia carriage on tick fitness will be assessed. 2) Examine the interaction between tick-derived molecules and SFG Rickettsia during infection in typical and atypical tick/Rickettsia relationships. Protein-protein interaction assays will be used to identify rickettsial binding proteins present in whole tick tissues. Studies will utilize paired tick tissues and SFG rickettsiae in comparative pull-down and protein binding assays. We will identify key tick proteins and delineate their role in the establishment of Rickettsia via bioassays including adhesion/invasion blocking assays, immune/antimicrobial activity assessment, and RNA-mediated interference (RNAi). The utilization of specific molecules by individual species of Rickettsia will also be assessed.

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 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 #
5R01AI077784-05
Application #
8511547
Study Section
Vector Biology Study Section (VB)
Program Officer
Perdue, Samuel S
Project Start
2009-08-20
Project End
2014-07-31
Budget Start
2013-08-01
Budget End
2014-07-31
Support Year
5
Fiscal Year
2013
Total Cost
$340,880
Indirect Cost
$110,556
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
Harris, Emma K; Jirakanwisal, Krit; Verhoeve, Victoria I et al. (2018) The role of Sca2 and RickA in the dissemination of Rickettsia parkeri in Amblyomma maculatum. Infect Immun :
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
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
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
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

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