BACKGROUND: Phlebotomus perniciosus is the main vector in the western Mediterranean area of the protozoan parasite Leishmania infantum, the causative agent of canine and human visceral leishmaniases. Infected dogs serve as a reservoir of the disease, and therefore measuring the exposure of dogs to sand fly bites is important for estimating the risk of L. infantum transmission. In bitten hosts, sand fly saliva elicits a specific antibody response that reflects the intensity of sand fly exposure. As screening of specific anti-saliva antibodies is limited by the availability of salivary gland homogenates, utilization of recombinant salivary proteins is a promising alternative. In this manuscript we show for the first time the use of recombinant salivary proteins as a functional tool for detecting P. perniciosus bites in dogs. METHODOLOGY/PRINCIPAL FINDINGS: The reactivity of six bacterially-expressed recombinant salivary proteins of P. perniciosus, yellow-related protein rSP03B, apyrases rSP01B and rSP01, antigen 5-related rSP07, ParSP25-like protein rSP08 and D7-related protein rSP04, were tested with sera of mice and dogs experimentally bitten by this sand fly using immunoblots and ELISA. In the immunoblots, both mice and canine sera gave positive reactions with yellow-related protein, both apyrases and ParSP25-like protein. A similar reaction for recombinant salivary proteins was observed by ELISA, with the reactivity of yellow-related protein and apyrases significantly correlated with the antibody response of mice and dogs against the whole salivary gland homogenate. CONCLUSIONS/SIGNIFICANCE: Three recombinant salivary antigens of P. perniciosus, yellow-related protein rSP03B and the apyrases rSP01B and rSP01, were identified as the best candidates for evaluating the exposure of mice and dogs to P. perniciosus bites. Utilization of these proteins, or their combination, would be beneficial for screening canine sera in endemic areas of visceral leishmaniases for vector exposure and for estimating the risk of L. infantum transmission in dogs.

Department of Parasitology Faculty of Science Charles University Prague Prague Czech Republic

Unidad de Entomología Médica Servicio de Parasitología Centro Nacional de Microbiología Instituto de Salud Carlos 3 Majadahonda Madrid Spain

Zobrazit více v PubMed

Baneth G, Koutinas AF, Solano-Gallego L, Bourdeau P, Ferrer L (2008) Canine leishmaniosis - new concepts and insights on an expanding zoonosis: part one. Trends Parasitol 24: 324–30. PubMed

Schantz PM, Steurer FJ, Duprey ZH, Kurpel KP, Barr SC, et al. (2005) Autochthonous visceral leishmaniasis in dogs in North America. J Am Vet Med Assoc 226: 1316–22. PubMed

Dujardin JC, Campino L, Canavate C, Dedet JP, Gradoni L, et al. (2008) Spread of vector-borne diseases and neglect of Leishmaniasis, Europe. Emerg Infect Dis 14: 1013–8. PubMed PMC

Carranza-Tamayo CO, Carvalho Mdo S, Bredt A, Bofil MI, Rodrigues RM, Silva AD, et al. (2010) Autochthonous visceral leishmaniasis in Brasilia, Federal District, Brazil. Rev Soc Bras Med Trop 43: 396–9. PubMed

Killick-Kendrick R (1999) The biology and control of phlebotomine sand flies. Clin Dermatol 17: 279–89. PubMed

Hostomska J, Rohousova I, Volfova V, Stanneck D, Mencke N, et al. (2008) Kinetics of canine antibody response to saliva of the sand fly Lutzomyia longipalpis. Vector Borne Zoonotic Dis 8: 443–50. PubMed

Vlkova M, Rohousova I, Drahota J, Stanneck D, Kruedewagen EM, et al. (2011) Canine antibody response to Phlebotomus perniciosus bites negatively correlates with the risk of Leishmania infantum transmission. PLoS Negl Trop Dis 5: e1344. PubMed PMC

Gomes RB, Mendonca IL, Silva VC, Ruas J, Silva MB, et al. (2007) Antibodies against Lutzomyia longipalpis saliva in the fox Cerdocyon thousand the sylvatic cycle of Leishmania chagasi. Trans R Soc Trop Med Hyg 101: 127–33. PubMed

Vlkova M, Rohousova I, Hostomska J, Pohankova L, Zidkova L, et al. (2012) Kinetics of antibody response in BALB/c and C57BL/6 mice bitten by Phlebotomus papatasi. PLoS Negl Trop Dis 6: e1719. PubMed PMC

Souza AP, Andrade BB, Aquino D, Entringer P, Miranda JC, et al. (2010) Using recombinant proteins from Lutzomyia longipalpis saliva to estimate human vector exposure in visceral Leishmaniasis endemic areas. PLoS Negl Trop Dis 4: e649. PubMed PMC

Teixeira C, Gomes R, Collin N, Reynoso D, Jochim R, et al. (2010) Discovery of markers of exposure specific to bites of Lutzomyia longipalpis, the vector of Leishmania infantum chagasi in Latin America. PLoS Negl Trop Dis 4: e638. PubMed PMC

Martin-Martin I, Molina R, Jimenez M (2012) An insight into the Phlebotomus perniciosus saliva by a proteomic approach. Acta Trop 123: 22–30. PubMed

Volf P, Volfova V (2011) Establishment and maintenance of sand fly colonies. J Vector Ecol 36 Suppl 1: S1–9. PubMed

Molina R (1991) Laboratory adaptation of an autochthonous colony of Phlebotomus perniciosus Newstead, 1911(Diptera: Psychodidae). Research and Reviews in Parasitology 51: 87–89.

Anderson JM, Oliveira F, Kamhawi S, Mans BJ, Reynoso D, et al. (2006) Comparative salivary gland transcriptomics of sandfly vectors of visceral leishmaniasis. BMC Genomics 7: 52. PubMed PMC

Rohousova I, Ozensoy S, Ozbel Y, Volf P (2005) Detection of species-specific antibody response of humans and mice bitten by sand flies. Parasitology 130: 493–9. PubMed

Drahota J, Lipoldova M, Volf P, Rohousova I (2009) Specificity of anti-saliva immune response in mice repeatedly bitten by Phlebotomus sergenti. Parasite Immunol 12: 766–70. PubMed

Ribeiro JM, Mans BJ, Arca B (2010) An insight into the sialome of blood-feeding Nematocera. Insect Biochem Mol Biol 40: 767–84. PubMed PMC

Oliveira F, Kamhawi S, Seitz AE, Pham VM, Guigal PM, et al. (2006) From transcriptome to immunome: identification of DTH inducing proteins from a Phlebotomus ariasi salivary gland cDNA library. Vaccine 24: 374–90. PubMed

Hostomska J, Volfova V, Mu J, Garfield M, Rohousova I, et al. (2009) Analysis of salivary transcripts and antigens of the sand fly Phlebotomus arabicus. BMC Genomics 10: 282. PubMed PMC

Rohousova I, Subrahmanyam S, Volfova V, Mu J, Volf P, Valenzuela JG, et al. (2012) Salivary gland transcriptomes and proteomes of Phlebotomus tobbi and Phlebotomus sergenti, vectors of leishmaniasis. PLoS Negl Trop Dis 6: e1660. PubMed PMC

Volf P, Skarupova S, Man P (2002) Characterization of the lectin from females of Phlebotomus duboscqi sand flies. Eur J Biochem 269: 6294–301. PubMed

Xu X, Oliveira F, Chang BW, Collin N, Gomes R, et al. (2011) Structure and function of a “yellow” protein from saliva of the sand fly Lutzomyia longipalpis that confers protective immunity against Leishmania major infection. J Biol Chem 286: 32383–93. PubMed PMC

Gomes R, Oliveira F, Teixeira C, Meneses C, Gilmore DC, et al. (2012) Immunity to sand fly salivary protein LJM11 modulates host response to vector-transmitted leishmania conferring ulcer-free protection. J Invest Dermatol 132: 2735–43. PubMed PMC

Martin-Martin I, Molina R, Jiménez M (2013) Molecular and Immunogenic Properties of Apyrase SP01B and D7-Related SP04 Recombinant Salivary Proteins of Phlebotomus perniciosus from Madrid, Spain. BioMed Research International 2013: 526069. PubMed PMC

Hamasaki Ryoichi, Kato Hirotomo, Terayama Yoshimi, Iwata Hiroyuki, Valenzuela Jesus G (2009) Functional characterization of a salivary apyrase from the sand fly, Phlebotomus duboscqi, a vector of Leishmania major. J Insect Physiol 55: 1044–1049. PubMed PMC

Ready PD (2010) Leishmaniasis emergence in Europe. Euro Surveill 15: 19505. PubMed

Maroli M, Rossi L, Baldelli R, Capelli G, Ferroglio E, et al. (2008) The northward spread of leishmaniasis in Italy: evidence from retrospective and ongoing studies on the canine reservoir and phlebotomine vectors. Trop Med Int Health 13: 256–64. PubMed

Baron SD, Morillas-Marquez F, Morales-Yuste M, Diaz-Saez V, Irigaray C, et al. (2011) Risk maps for the presence and absence of Phlebotomus perniciosus in an endemic area of leishmaniasis in southern Spain: implications for the control of the disease. Parasitology 138: 1234–44. PubMed

Hartemink N, Vanwambeke SO, Heesterbeek H, Rogers D, Morley D, et al. (2011) Integrated mapping of establishment risk for emerging vector-borne infections: a case study of canine leishmaniasis in southwest France. PLoS One 6: e20817. PubMed PMC

Branco S, Alves-Pires C, Maia C, Cortes S, Cristovao JM, et al. (2013) Entomological and ecological studies in a new potential zoonotic leishmaniasis focus in Torres Novas municipality, Central Region, Portugal. Acta Trop 125: 339–48. PubMed

Volf P, Rohousova I (2001) Species-specific antigens in salivary glands of phlebotomine sandflies. Parasitology 122: 37–41. PubMed

Boggiatto PM, Gibson-Corley KN, Metz K, Gallup JM, Hostetter JM, et al. (2011) Transplacental transmission of Leishmania infantum as a means for continued disease incidence in North America. PLoS Negl Trop Dis 5 (4) e1019. PubMed PMC

Assessment of the exposure to Phlebotomus perniciosus and the presence of anti-Leishmania infantum antibodies in stray cats in an endemic region of Spain, and their potential correlation with environmental factors

Exposure to Phlebotomus perniciosus sandfly vectors is positively associated with Toscana virus and Leishmania infantum infection in human blood donors in Murcia Region, southeast Spain

Phlebotomus perniciosus Recombinant Salivary Proteins Polarize Murine Macrophages Toward the Anti-Inflammatory Phenotype

Monitoring Leishmania infection and exposure to Phlebotomus perniciosus using minimal and non-invasive canine samples

Synthetic peptides as a novel approach for detecting antibodies against sand fly saliva

Human antibody reaction against recombinant salivary proteins of Phlebotomus orientalis in Eastern Africa

Seasonal dynamics of canine antibody response to Phlebotomus perniciosus saliva in an endemic area of Leishmania infantum

Evaluation of the rSP03B sero-strip, a newly proposed rapid test for canine exposure to Phlebotomus perniciosus, vector of Leishmania infantum

Insights into the sand fly saliva: Blood-feeding and immune interactions between sand flies, hosts, and Leishmania

Recombinant Salivary Proteins of Phlebotomus orientalis are Suitable Antigens to Measure Exposure of Domestic Animals to Sand Fly Bites

Canine Antibodies against Salivary Recombinant Proteins of Phlebotomus perniciosus: A Longitudinal Study in an Endemic Focus of Canine Leishmaniasis

Zobrazit více v PubMed

GENBANK
KF257364, KF257365, KF257366, KF257367, KF257368, KF257369