Ixodes scapularis ticks overwinter in the Northeast and Upper Midwest parts of United States, and transmit various human pathogens that include human anaplasmosis agent Anaplasma phagocytophilum. My preliminary data show that the presence of A. phagocytophilum in ticks increases the ability of I. scapularis to survive in the cold. I have identified an I. scapularis antifreeze glycoprotein, designated as IAFGP and demonstrate, via RNAi knockdown studies, the importance of IAFGP for the survival of ticks in a freezing environment. Transfection studies also show that IAFGP increases the viability of yeast cells subjected to low temperatures. Remarkably, I have found that A. phagocytophilum induce the expression of iafgp and thereby increase the cold tolerance of I. scapularis. These data define a molecular basis for symbiosis between A. phagocytophilum and I. scapularis. The mechanism by which A. phagocytophilum, induce iafgp expression is not understood. Therefore studies will be performed to elucidate the mechanism by which A. phagocytophilum influence vector gene expression for its own benefit as well as its vector host survival during freezing temperatures. Following are the specific aims that will be addressed to understand the mechanism:
In aim 1, I will identify and characterize iafgp promoter in I. scapularis. The studies in this aim will address whether iafgp promoter is activated upon A. phagocytophilum infection.
In aim 2, studies will be undertaken to characterize the role of host transcriptional activators that may be involved in iafgp promoter induction. Collectively, the proposed studies not only elucidate the molecular mechanisms of symbiotic association between A. phagocytophilum and I. scapularis ticks but also delineate a new approach to study host-pathogen interaction.

Public Health Relevance

In United States, the life-cycle of Ixodes scapularis ticks that transmit several human pathogens involves overwintering stages. My previous studies show that a human pathogenic bacterium A. phagocytophilum establishes a symbiotic relationship with its arthropod vector to enhance survival in the cold, via the selective induction of a novel antifreeze glycoprotein (iafgp) in Ixodes scapularis. The goal of this proposal is to understand the mechanism by which A. phagocytophilum up-regulate iafgp gene expression for its own benefit and for its vector host survival in the cold temperature.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Small Research Grants (R03)
Project #
7R03AI090197-03
Application #
8578755
Study Section
Vector Biology Study Section (VB)
Program Officer
Mukhopadhyay, Suman
Project Start
2011-03-01
Project End
2014-02-28
Budget Start
2012-10-19
Budget End
2014-02-28
Support Year
3
Fiscal Year
2012
Total Cost
$42,147
Indirect Cost
$14,600
Name
Old Dominion University
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
041448465
City
Norfolk
State
VA
Country
United States
Zip Code
23508
Neelakanta, Girish; Sultana, Hameeda (2015) Transmission-Blocking Vaccines: Focus on Anti-Vector Vaccines against Tick-Borne Diseases. Arch Immunol Ther Exp (Warsz) 63:169-79