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Inhibitory effect of cyclophilin A from the hard tick Haemaphysalis longicornis on the growth of Babesia bovis and Babesia bigemina

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Abstract

Haemaphysalis longicornis is known as one of the most important ticks transmitting Babesia parasites in East Asian countries, including Babesia ovata and Babesia gibsoni, as well as Theileria parasites. H. longicornis is not the natural vector of Babesia bovis and Babesia bigemina. Vector ticks and transmitted parasites are thought to have established unique host–parasite interaction for their survival, meaning that vector ticks may have defensive molecules for the growth control of parasites in their bodies. However, the precise adaptation mechanism of tick-Babesia parasites is still unknown. Recently, cyclophilin A (CyPA) was reported to be important for the development of Babesia parasites in ticks. To reveal a part of their adaptation mechanism, the current study was conducted. An injection of B. bovis-infected RBCs into adult female H. longicornis ticks was found to upregulate the expression profiles of the gene and protein of CyPA in H. longicornis (HlCyPA). In addition, recombinant HlCyPA (rHlCyPA) purified from Escherichia coli exhibited significant inhibitory growth effects on B. bovis and B. bigemina cultivated in vitro, without any hemolytic effect on bovine RBCs at all concentrations used. In conclusion, our results suggest that HlCyPA might play an important role in the growth regulation of Babesia parasites in H. longicornis ticks, during natural acquisition from an infected host. Furthermore, rHlCyPA may be a potential alternative chemotherapeutic agent against babesiosis.

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References

  • AbouLaila M, Sivakumar T, Yokoyama N, Igarashi I (2010) Inhibitory effect of terpene nerolidol on the growth of Babesia parasites. Parasitol Int 59:278–282

    Article  PubMed  CAS  Google Scholar 

  • Adham FK, Abd-el-Samie EM, Gabre RM, el-Hussein H (2009) Detection of tick blood parasites in Egypt using PCR assay I-Babesia bovis and Babesia bigemina. Parasitol Res 105:721–730

    Article  PubMed  CAS  Google Scholar 

  • Aung KM, Boldbaatar D, Umemiya-Shirafuji R, Liao M, Tsuji N, Xuan X, Suzuki H, Kume A, Galay RL, Tanaka T, Fujisaki K (2012) HlSRB, a Class B scavenger receptor, is key to the granulocyte-mediated microbial phagocytosis in ticks. PLoS One 7:e33504

    Article  PubMed  CAS  Google Scholar 

  • Barik S (2006) Immunophilins: for the love of proteins. Cell Mol Life Sci 63:2889–2900

    Article  PubMed  CAS  Google Scholar 

  • Bastos RG, Ueti MW, Guerrero FD, Knowles DP, Scoles GA (2009) Silencing of a putative immunophilin gene in the cattle tick Rhipicephalus (Boophilus) microplus increases the infection rate of Babesia bovis in larval progeny. Parasit Vectors 2:57

    Article  PubMed  Google Scholar 

  • Bell A, Monaghan P, Page AP (2006) Peptidyl-prolyl cis–trans isomerases (immunophilins) and their roles in parasite biochemistry, host–parasite interaction and antiparasitic drug action. Int J Parasitol 36:261–276

    Article  PubMed  CAS  Google Scholar 

  • Bock R, Jackson L, De Vos A, Jorgensen W (2004) Babesiosis of cattle. Parasitology 129:S247–S269

    Article  PubMed  Google Scholar 

  • Boldbaatar D, Kilonzo RM, Battur B, Umemiya R, Liao M, Tanaka T, Xuan X, Fujisaki K (2008) Identification of two forms of cyclophilin from the hard tick Haemaphysalis longicornis. Process Biochem 43:615–625

    Article  CAS  Google Scholar 

  • Bork S, Yokoyama N, Matsuo T, Claveria FG, Fujisaki K, Igarashi I (2003) Growth inhibitory effect of triclosan on equine and bovine Babesia parasites. AmJTrop Med Hyg 68:334–340

    CAS  Google Scholar 

  • Bork S, Yokoyama N, Ikehara Y, Kumar S, Sugimoto C, Igarashi I (2004) Growth-inhibitory effect of heparin on Babesia parasites. Antimicrob Agents Chemother 48:236–241

    Article  PubMed  CAS  Google Scholar 

  • Chauvin A, Moreau E, Bonnet S, Plantard O, Malandrin L (2009) Babesia and its hosts: adaptation to long-lasting interactions as a way to achieve efficient transmission. Vet Res 40:37

    Article  PubMed  Google Scholar 

  • Florin-Christensen M, Schnittger L (2009) Piroplasmids and ticks: a long-lasting intimate relationship. Front Biosci 14:3064–3073

    Article  PubMed  CAS  Google Scholar 

  • Fujisaki K (1978) Development of acquired resistance precipitating antibody in rabbits experimentally infested with females of Haemaphysalis longicornis (Ixodoidea: Ixodidae). Natl Inst Anim Health Q (Tokyo) 18:27–38

    CAS  Google Scholar 

  • Galat A (1993) Peptidylproline cis–trans isomerases: immunophilins. Eur J Biochem 216:689–707

    Article  PubMed  CAS  Google Scholar 

  • Galat A (2004) Function-dependent clustering of orthologues and paralogues of cyclophilins. Proteins 56:808–820

    Article  PubMed  CAS  Google Scholar 

  • Galay RL, Maeda H, Aung KM, Umemiya-Shirafuji R, Xuan X, Igarashi I, Tsuji N, Tanaka T, Fujisaki K (2012) Anti-babesial activity of a potent peptide fragment derived from longicin of Haemaphysalis longicornis. Trop Anim Health Prod 44:343–348

    Article  PubMed  Google Scholar 

  • Goo YK, Terkawi MA, Jia H, Aboge GO, Ooka H, Nelson B, Kim S, Sunaga F, Namikawa K, Igarashi I, Nishikawa Y, Xuan X (2010) Artesunate, a potential drug for treatment of Babesia infection. Parasitol Int 59:481–486

    Article  PubMed  CAS  Google Scholar 

  • Homer MJ, Aguilar-Delfin I, Telford SR 3rd, Krause PJ, Persing DH (2000) Babesiosis. Clin Microbiol Rev 13:451–469

    Article  PubMed  CAS  Google Scholar 

  • Hubálek Z, Rudolf I (2012) Tick-borne viruses in Europe. Parasitol Res 1:9–36

    Article  Google Scholar 

  • Krücken J, Greif G, von Samson-Himmelstjerna G (2009) In silico analysis of the cyclophilin repertoire of apicomplexan parasites. Parasit Vectors 2:27

    Article  PubMed  Google Scholar 

  • Laemmli UK (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227:680–685

    Article  PubMed  CAS  Google Scholar 

  • Liu X, Sun L, Yu M, Wang Z, Xu C, Xue Q, Zhang K, Ye X, Kitamura Y, Liu W (2009) Cyclophilin A interacts with influenza A virus M1 protein and impairs the early stage of the viral replication. Cell Microbiol 11:730–741

    Article  PubMed  CAS  Google Scholar 

  • Liu X, Zhao Z, Xu C, Sun L, Chen J, Zhang L, Liu W (2012) Cyclophilin A restricts influenza A virus replication through degradation of the M1 protein. PLoS One 7:e31063

    Article  PubMed  CAS  Google Scholar 

  • Luban J (2007) Cyclophilin A, TRIM5, and resistance to human immunodeficiency virus type 1 infection. J Virol 81:1054–1061

    Article  PubMed  CAS  Google Scholar 

  • Nagai A, Yokoyama N, Matsuo T, Bork S, Hirata H, Xuan X, Zhu Y, Claveria FG, Fujisaki K, Igarashi I (2003) Growth-inhibitory effects of artesunate, pyrimethamine, and pamaquine against Babesia equi and Babesia caballi in in vitro cultures. Antimicrob Agents Chemother 47:800–803

    Article  PubMed  CAS  Google Scholar 

  • Nagy PD, Wang RY, Pogany J, Hafren A, Makinen K (2011) Emerging picture of host chaperone and cyclophilin roles in RNA virus replication. Virology 411:374–382

    Article  PubMed  CAS  Google Scholar 

  • Rahman M, Tsuji N, Boldbaatar D, Battur B, Liao M, Umemiya-Shirafuji R, You M, Tanaka T, Fujisaki K (2010) Structural characterization and cytolytic activity of a potent antimicrobial motif in longicin, a defensin-like peptide in the tick Haemaphysalis longicornis. J Vet Med Sci 72:149–156

    Article  PubMed  CAS  Google Scholar 

  • Salama AA, Aboulaila M, Moussa AA, Nayel MA, El-Sify A, Terkawi MA, Hassan HY, Yokoyama N, Igarashi I (2012) Evaluation of in vitro and in vivo inhibitory effects of fusidic acid on Babesia and Theileria parasites. Vet Parasitol (in press)

  • Schnittger L, Rodriguez AE, Florin-Christensen M, Morrison DA (2012) Babesia: a world emerging. Infect Genet Evol 12:1788–1809

    Article  PubMed  Google Scholar 

  • Sonenshine DE, Hynes WL (2008) Molecular characterization and related aspects of the innate immune response in ticks. Front Biosci 13:7046–7063

    Article  PubMed  CAS  Google Scholar 

  • Stark M, Liu LP, Deber CM (2002) Cationic hydrophobic peptides with antimicrobial activity. Antimicrob Agents Chemother 46:3585–3590

    Article  PubMed  CAS  Google Scholar 

  • Tanaka T, Maeda H, Matsuo T, Boldbattar D, Umemiya-Shirafuji R, Kume A, Suzuki H, Xuan X, Tsuji N, Fujisaki (2012) Parasiticidal activity of Haemaphysalis longicornis longicin P4 peptide against Toxoplasma gondii. Peptides 34:242–250

    Article  PubMed  CAS  Google Scholar 

  • Tsuji N, Battsetseg B, Boldbaatar D, Miyoshi T, Xuan X, Oliver JH Jr, Fujisaki K (2007) Babesial vector tick defensin against Babesia sp. parasites. Infect Immun 75:3633–3640

    Article  PubMed  CAS  Google Scholar 

  • Tsuji N, Miyoshi T, Battsetseg B, Matsuo T, Xuan X, Fujisaki K (2008) A cysteine protease is critical for Babesia spp. transmission in Haemaphysalis longocornis ticks. PLoS Pathog 4:e1000062

    Article  PubMed  Google Scholar 

  • Umemiya-Shirafuji R, Tanaka T, Boldbaatar D, Tanaka T, Fujisaki K (2012) Akt is an essential player in regulating cell/organ growth at the adult stage in the hard tick Haemaphysalis longicornis. Insect Biochem Mol Biol 42:164–173

    Article  PubMed  CAS  Google Scholar 

  • Vannier E, Gewurz BE, Krause PJ (2008) Human babesiosis. Infect Dis Clin North Am 22:469–488

    Article  PubMed  Google Scholar 

  • Xu C, Meng S, Liu X, Sun L, Liu W (2010) Chicken cyclophilin A is an inhibitory factor to influenza virus replication. Virol J 7:372

    Article  PubMed  CAS  Google Scholar 

  • Zhou D, Mei Q, Li J, He H (2012) Cyclophilin A and viral infections. Biochem Biophys Res Commun 424:647–650

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We are grateful to Dr. C. Kubota, Laboratory of Veterinary Theriogenology, Department of Clinical Veterinary Science, Joint Faculty of Veterinary Medicine, Kagoshima University, and Dr. H. Yamaguchi, Iriki Livestock Farm, Joint Faculty of Veterinary Medicine, Kagoshima University, for the supply of bovine blood. This work was supported by the Bio-oriented Technology Research Advancement Institution (BRAIN) and Grants-in-Aid for Scientific Research (A) and (C) from the Japan Society for the Promotion of Science (JSPS).

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Correspondence to Tetsuya Tanaka.

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Maeda, H., Boldbaatar, D., Kusakisako, K. et al. Inhibitory effect of cyclophilin A from the hard tick Haemaphysalis longicornis on the growth of Babesia bovis and Babesia bigemina . Parasitol Res 112, 2207–2213 (2013). https://doi.org/10.1007/s00436-013-3390-7

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  • DOI: https://doi.org/10.1007/s00436-013-3390-7

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