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Anaplasma phagocytophilum modulate tick gene expression for its survival and transmission from the vector host

Award Number: R01AI130116
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Project Summary/Abstract Human anaplasmosis, caused by the obligate intracellular bacterium Anaplasma phagocytophilum, is one of the most common tick-borne diseases in the United States. In mammals and ticks, A. phagocytophilum resides in neutrophils and in salivary glands, respectively. Despite numerous studies that have focused on understanding strategies that A. phagocytophilum uses to survive in the mammalian cells, relatively few studies have clearly defined the molecular strategies that A. phagocytophilum uses to survive in ticks. In this project, we will be performing a comprehensive molecular analysis on Ixodes scapularis organic anion transporting polypeptides (OATPs) and genes involved in the tryptophan metabolism pathway in A. phagocytophilum-tick interactions. This study is build upon our efforts in showing how A. phagocytophilum modulates gene expression and cell signaling for its survival in the vector. As an example, our previous studies has shown that A. phagocytophilum modulate tick antifreeze gene expression and actin phosphorylation for its survival in the vector. Here, we provide strong preliminary in vitro and in vivo data showing that A. phagocytophilum induces expression of a specific OATP (OATP4056) and kynurenine aminotransferase (KAT), a gene involved in the tryptophan pathway. We now hypothesize that interplay between OATP4056 and KAT not only facilitates A. phagocytophilum survival in the vector but also aid in the transmission of this bacterium to a vertebrate host. RNAi analysis revealed that knockdown of OATP4056 has no effect on A. phagocytophilum acquisition but affected its survival and transmission from these ticks. Electrophoretic mobility shift assays with promoter region and total lysates prepared from uninfected and A. phagocytophilum-infected ticks provide further evidence that the presence of this bacterium influences expression of OATP4056 in these ticks. In addition, we found evidence that a metabolite from tryptophan pathway regulates A. phagocytophilum survival and OATP4056 gene expression in these ticks. These results provide important insights for our proposed studies to define molecular basis of the relationship of A. phagocytophilum with ticks. Based on our strong preliminary results and the experiments proposed, we believe that this could be a transformative study that not only serves as a model to study intimate relationships established by pathogens with their arthropod vectors but may also lead in the development of new strategies to interrupt the transmission of this and perhaps other Rickettsial species of medical importance.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2023 ( Subtotal = $0 )
2023	2021	UNIVERSITY OF TENNESSEE	201 ANDY HOLT TOWER	KNOXVILLE	TN	37996	KNOX	USA	Allergy and Infectious Diseases Research	000	6	5/31/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = -$214 )
2022	2019	OLD DOMINION UNIVERSITY	5115 HAMPTON BLVD	NORFOLK	VA	23529	NORFOLK CITY	USA	Allergy and Infectious Diseases Research	002	3	6/29/2022	NON-COMPETING CONTINUATION	-$214
2022	2018	OLD DOMINION UNIVERSITY	5115 HAMPTON BLVD	NORFOLK	VA	23529	NORFOLK CITY	USA	Allergy and Infectious Diseases Research	001	2	6/29/2022	NON-COMPETING CONTINUATION	$0
2022	2017	OLD DOMINION UNIVERSITY	5115 HAMPTON BLVD	NORFOLK	VA	23529	NORFOLK CITY	USA	Allergy and Infectious Diseases Research	000	1	6/29/2022	NEW	$0
														Subtotal = -$214

Issue Date FY: 2021 ( Subtotal = $337,500 )
2021	2021	UNIVERSITY OF TENNESSEE	1331 CIR PARK DR	KNOXVILLE	TN	37916	KNOX	USA	Allergy and Infectious Diseases Research	002	6	6/3/2021	NON-COMPETING CONTINUATION	$362,500
2021	2020	UNIVERSITY OF TENNESSEE	1331 CIR PARK DR	KNOXVILLE	TN	37916	KNOX	USA	Allergy and Infectious Diseases Research	004	5	9/2/2021	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$223,477
2021	2020	OLD DOMINION UNIVERSITY	5115 HAMPTON BLVD	NORFOLK	VA	23529	NORFOLK CITY	USA	Allergy and Infectious Diseases Research	000	4	3/18/2021	NON-COMPETING CONTINUATION	-$387,500
2021	2020	UNIVERSITY OF TENNESSEE	1331 CIR PARK DR	KNOXVILLE	TN	37916	KNOX	USA	Allergy and Infectious Diseases Research	001	5	3/18/2021	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$362,500
2021	2019	OLD DOMINION UNIVERSITY	5115 HAMPTON BLVD	NORFOLK	VA	23529	NORFOLK CITY	USA	Allergy and Infectious Diseases Research	003	3	9/2/2021	NON-COMPETING CONTINUATION	-$223,477
														Subtotal = $337,500

Issue Date FY: 2020 ( Subtotal = $387,500 )
2020	2020	OLD DOMINION UNIVERSITY	5115 HAMPTON BLVD	NORFOLK	VA	23529	NORFOLK CITY	USA	Allergy and Infectious Diseases Research	000	4	6/26/2020	NON-COMPETING CONTINUATION	$387,500
														Subtotal = $387,500

Issue Date FY: 2019 ( Subtotal = $387,500 )
2019	2019	OLD DOMINION UNIVERSITY	5115 HAMPTON BLVD	NORFOLK	VA	23529	NORFOLK CITY	USA	Allergy and Infectious Diseases Research	000	3	6/17/2019	NON-COMPETING CONTINUATION	$387,500
														Subtotal = $387,500

Issue Date FY: 2018 ( Subtotal = $387,500 )
2018	2018	OLD DOMINION UNIVERSITY	5115 HAMPTON BLVD	NORFOLK	VA	23529	NORFOLK CITY	USA	Allergy and Infectious Diseases Research	000	2	5/24/2018	NON-COMPETING CONTINUATION	$387,500
														Subtotal = $387,500

Issue Date FY: 2017 ( Subtotal = $387,500 )
2017	2017	OLD DOMINION UNIVERSITY	5115 HAMPTON BLVD	NORFOLK	VA	23529	NORFOLK CITY	USA	Allergy and Infectious Diseases Research	000	1	7/18/2017	NEW	$387,500
														Subtotal = $387,500

Grand Total All Awards = $1,887,286

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Anaplasma phagocytophilum modulate tick gene expression for its survival and transmission from the vector host

Award Number: R01AI130116

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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