Abstract
Subolesin was recently shown by both gene silencing and immunization with the recombinant protein to protect against tick infestations, and to cause reduced tick survival and degeneration of gut and salivary gland tissues. In this research, we extended these studies by testing whether targeting subolesin by RNAi or vaccination interfered with the ability of ticks to become infected with two tick-borne pathogens, Anaplasma marginale which causes bovine anaplasmosis and Anaplasma phagocytophilum, the causative agent of human granulocytin anaplasmosis. For the A. marginale studies, Dermacentor variabilis males were injected with subolesin dsRNA or saline and then were allowed to feed on cattle with ascending rickettsemias, while for the A. phagocytophilum studies, mice were immunized with the recombinant subolesin protein, infected with the pathogen and then infested with larval Ixodes scapularis. Tick infections were determined by quantitative polymerase chain reaction of gut and salivary gland tissues. In both experimental approaches, tick infections were significantly reduced. These results suggest that subolesin appears to be a candidate vaccine antigen that may contribute to control of multiple tick species and the reduction of tick-borne pathogens.


Similar content being viewed by others
References
Almazán C, Kocan KM, Bergman DK, Garcia-Garcia JC, Blouin EF, de la Fuente J (2003a) Identification of protective antigens for the control of Ixodes scapularis infestations using cDNA expression library immunization. Vaccine 21:1492–1501
Almazán C, Kocan KM, Bergman DK, Garcia-Garcia JC, Blouin EF, de la Fuente J (2003b) Characterization of genes transcribed in an Ixodes scapularis cell line that were identified by expression library immunization and analysis of expressed sequence tags. Gene Ther Mol Biol 7:43–59
Almazán C, Blas-Machado U, Kocan KM, Yoshioka JH, Blouin EF, Mangold AJ, de la Fuente J (2005a) Characterization of three Ixodes scapularis cDNAs protective against tick infestations. Vaccine 23:4403–4416
Almazán C, Kocan KM, Blouin EF, de la Fuente J (2005b) Vaccination with recombinant tick antigens for the control of Ixodes scapularis adult infestations. Vaccine 23:5294–5298
Asanovich KM, Bakken JS, Madigan JE, Aguero-Rosenfeld M, Wormser GP, Dumler JS (1997) Antigenic diversity of granulocytic Ehrlichia isolates from humans in Wisconsin and New York and a horse in California. J Infect Dis 176:1029–1034
de la Fuente J, Kocan KM (2003) Advances in the identification and characterization of protective antigens for development of recombinant vaccines against tick infestations. Expert Rev Vaccines 2:583–593
de la Fuente J, Kocan KM (2006) Strategies for development of vaccines for control of ixodid tick species. Parasite Immunol (in press). DOI 10.1111/j.1365-3024.2006.00828.x
de la Fuente J, Garcia-Garcia JC, Blouin EF, Kocan KM (2001) Major surface protein 1a effects tick infection and transmission of the ehrlichial pathogen Anaplasma marginale. Int J Parasitol 31:1705–1714
de la Fuente J, García-García JC, Blouin EF, Saliki JT, Kocan KM (2002) Infection of tick cells and bovine erythrocytes with one genotype of the intracellular ehrlichia Anaplasma marginale excludes infection with other genotypes. Clin Diagn Lab Immunol 9:658–668
de la Fuente J, Almazán C, Blouin EF, Naranjo V, Kocan KM (2005a) RNA interference screening in ticks for identification of protective antigens. Parasitol Res 96:137–141
de la Fuente J, Ayoubi P, Blouin EF, Almazán C, Naranjo V, Kocan KM (2005b) Gene expression profiling of human promyelocytic cells in response to infection with Anaplasma phagocytophilum. Cell Microbiol 7:549–559
de la Fuente J, Massung RF, Wong SJ, Chu FK, Lutz H, Meli M, von Loewenich FD, Grzeszczuk A, Torina A, Caracappa S, Mangold AJ, Naranjo V, Stuen S, Kocan KM (2005c) Sequence analysis of the msp4 gene of Anaplasma phagocytophilum strains. J Clin Microbiol 43:1309–1317
de la Fuente J, Almazán C, Blas-Machado U, Naranjo V, Mangold AJ, Blouin EF, Gortazar C, Kocan KM (2006a) The tick protective antigen, 4D8, is a conserved protein involved in modulation of tick blood digestion and reproduction. Vaccine 24:4082–4095
de la Fuente J, Almazán C, Naranjo V, Blouin EF, Kocan KM (2006b) Synergistic effect of silencing the expression of tick protective antigens 4D8 and Rs86 in Rhipicephalus sanguineus by RNA interference. Parasitol Res 99:108–113
de la Fuente J, Almazán C, Naranjo V, Blouin EF, Meyer JM, Kocan KM (2006c) Autocidal control of ticks by silencing of a single gene by RNA interference. Biochem Biophys Res Comm 344:332–338
Estrada-Peña A, Jongejan F (1999) Ticks feeding on humans: a review of records on human-biting Ixodoidea with special reference to pathogen transmission. Exp Appl Acarol 23:685–715
Gomes-Solecki MJC, Brisson DR, Dattwyler RJ (2005) Oral vaccine that breaks the transmission cycle of the Lyme disease spirochete can be delivered via bait. Vaccine 24(20):4440–4449
Goodman JL, Nelson C, Vitale B, Madigan JE, Dumler JS, Kurtti TJ, Munderloh UG (1996) Direct cultivation of the causative agent of human granulocytic ehrlichiosis. N Engl J Med 334:209–215
Kocan KM, Hair JA, Ewing SA (1980) Ultrastructure of Anaplasma marginale Theiler in Dermacentor andersoni Stiles and Dermacentor variabilis (Say). Am J Vet Res 41:1966–1976
Kocan KM, Stiller D, Goff WL, Claypool PL, Edwards W, Ewing SA, Mcguire TC, Hair JA, Barron SJ (1992a) Development of Anaplasma marginale in male Dermacentor andersoni transferred from parasitemic to susceptible cattle. Am J Vet Res 53:499–507
Kocan KM, Goff WL, Stiller D, Claypool PL, Edwards W, Ewing SA, Hair JA, Barron SJ (1992b) Persistence of Anaplasma marginale (Rickettsiales: Anaplasmataceae) in male Dermacentor andersoni (Acari: Ixodidae) transferred successively from infected to susceptible calves. J Med Entomol 29:657–668
Kocan K, de la Fuente J, Blouin EF, Garcia-Garcia JC (2004) Anaplasma marginale (Rickettsiales: Anaplasmataceae): recent advances in defining host-pathogen adaptations of a tick-borne rickettsia. Parasitology 129:S285–S300
Kocan KM, Yoshioka J, Sonenshine DE, de la Fuente J, Ceraul SM, Blouin EF, Almazán C (2005) Capillary tube feeding system for studying tick-pathogen interactions of Dermacentor variabilis (Acari: Ixodidae) and Anaplasma marginale (Rickettsiales: Anaplasmataceae). J Med Entomol 42:864–874
Labuda M, Trimnell AR, Lickova M, Kazimirova M, Davies GM, Lissina O, Hails RS, Nuttall PA (2006) An antivector vaccine protects against a lethal vector-borne pathogen. PLoS Pathog 2(4):e27
Pal U, Li X, Wang T, Montgomery RR, Ramamoorthi N, Desilva AM, Bao F, Yang X, Pypaert M, Pradhan D, Kantor FS, Telford S, Anderson JF, Fikrig E (2004) TROSPA, an Ixodes scapularis receptor for Borrelia burgdorferi. Cell 119:457–468
Parola P, Raoult D (2001) Tick-borne bacterial diseases emerging in Europe. Clin Microbiol Infect 7:80–83
Telford SR III, Dawson JE, Katavolos P, Warner CK, Kolbert CP, Persing DH (1996) Perpetuation of the agent of human granulocytic ehrlichiosis in a deer tick-rodent cycle. Proc Natl Acad Sci USA 93:6209–6214
Tsao JI, Wootton JT, Bunikis J, Luna MG, Fish D, Barbour AG (2004) An ecological approach to preventing human infection: vaccinating wild mouse reservoirs intervenes in the Lyme disease cycle. Proc Natl Acad Sci USA 101:18159–18164
Willadsen P (2004) Anti-tick vaccines. Parasitology 129:S1–S21
Acknowledgements
This research was supported by the Oklahoma Agricultural Experiment Station (project 1669), the Sitlington Endowed Chair for Food Animal Research (K. M. Kocan, Oklahoma State University). Consuelo Almazán was funded by Pfizer Animal Health, Kalamazoo, MI, and a grant-in-aid from the CONACYT and Promep (University of Tamaulipas), Mexico. V. Naranjo was founded by Consejería de Educación, JCCM, Spain. We thank Dollie Clawson for excellent technical assistance. These experiments comply with the current laws of the USA.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
de la Fuente, J., Almazán, C., Blouin, E.F. et al. Reduction of tick infections with Anaplasma marginale and A. phagocytophilum by targeting the tick protective antigen subolesin. Parasitol Res 100, 85–91 (2006). https://doi.org/10.1007/s00436-006-0244-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00436-006-0244-6