Ixodes scapularis ticks transmit Borrelia burgdorferi as well as several other pathogens of public health importance. Feeding ticks cut into host tissues and create a feeding pool from which they continuously feed for days. Host immune responses interfere with tick feeding by clogging the feeding site and producing molecules that are noxious to the tick. The host complement system is likely to pose special problems for feeding ticks because complement can directly damage non-self tissue as well as recruit arms of the immune response. The focus of this proposal is anti-complement proteins produced by I. scapularis. We plan to test the hypothesis that anti-complement proteins facilitate tick feeding and pathogen transmission.
Under aim 1 of the proposal we plan to functionally characterize two novel proteins designated Salp9 and Salp20 that are highly homologous to a known tick anti-complement protein.
Under aim 2 we propose to screen tick cDNA libraries prepared from salivary glands and guts for novel anti-complement proteins. Proteins produced by ticks are attractive vaccine targets because such vaccines have the potential to block tick feeding and pathogen transmission.
Under aim 3 we plan to test anti-complement proteins as vaccines that block feeding and/or pathogen transmission. Our industry partner in these studies is L2 diagnostics, which will assist with further development of tick anti-complement proteins as drugs and vaccines.
| de Silva, Aravinda Manu; Tyson, Katharine Rose; Pal, Utpal (2009) Molecular characterization of the tick-Borrelia interface. Front Biosci (Landmark Ed) 14:3051-63 |
| Tyson, Katharine R; Elkins, Christopher; de Silva, Aravinda M (2008) A novel mechanism of complement inhibition unmasked by a tick salivary protein that binds to properdin. J Immunol 180:3964-8 |
| Tyson, K; Elkins, C; Patterson, H et al. (2007) Biochemical and functional characterization of Salp20, an Ixodes scapularis tick salivary protein that inhibits the complement pathway. Insect Mol Biol 16:469-79 |
