Probiotics and Antimicrobial Proteins

, Volume 4, Issue 3, pp 208–216 | Cite as

Cyto-Insectotoxin 1a from Lachesana tarabaevi Spider Venom Inhibits Chlamydia trachomatis Infection

  • Nadezhda F. Polina
  • Marina M. Shkarupeta
  • Anna S. Popenko
  • Alexander A. Vassilevski
  • Sergey A. Kozlov
  • Eugene V. Grishin
  • Vassili N. Lazarev
  • Vadim M. Govorun


Venom of the ant spider Lachesana tarabaevi contains a wide variety of antimicrobial peptides. Among them, a special place belongs to cyto-insectotoxins, a class of cytolytic molecules showing equally potent antimicrobial and insecticidal effects. We tested one of them, CIT 1a, for ability to suppress Chlamydia trachomatis infection. HEK293 cells were transfected with plasmid vectors harboring the cit 1a gene. Controlled expression of the transgene led to a significant decrease in C. trachomatis viability inside the infected cells. Using proteomic and transcriptomic approaches, we found alterations in protein expression patterns and identified differentially expressed genes in transfected cells.


Antimicrobial peptide Cytolytic peptide Infectious disease Gene therapy Proteomics Transcriptome 



We are grateful to Irina Demina and Maria Galyamina from the Research Institute for Physico-Chemical Medicine, Moscow, for proteomic experiments. We thank Dr. Eva Hjelm (Uppsala University, Sweden) for the provided Chlamydia strain. Microarray experiments were carried out at ZAO “Genoanalytica”, Moscow, Russia. This work was funded by the Russian Foundation for Basic Research (grant number 11-04-00706) and the Program of Cell and Molecular Biology of the Russian Academy of Sciences.


  1. 1.
    Atkinson TP, Balish MF, Waites KB (2008) Epidemiology, clinical manifestations, pathogenesis and laboratory detection of Mycoplasma pneumoniae infections. FEMS Microbiol Rev 32:956–973CrossRefGoogle Scholar
  2. 2.
    Aziz MA, Wright A (2005) The World Health Organization/International Union against tuberculosis and lung disease global project on surveillance for anti-tuberculosis drug resistance: a model for other infectious diseases. Clin Infect Dis 41(Suppl 4):S258–S262CrossRefGoogle Scholar
  3. 3.
    Byrne GI, Ojcius DM (2004) Chlamydia and apoptosis: life and death decisions of an intracellular pathogen. Nat Rev Microbiol 2:802–808CrossRefGoogle Scholar
  4. 4.
    Caldwell HD, Kromhout J, Schachter J (1981) Purification and partial characterization of the major outer membrane protein of Chlamydia trachomatis. Infect Immun 31:1161–1176Google Scholar
  5. 5.
    Cao B, Zhao CJ, Yin YD, Zhao F, Song SF, Bai L, Zhang JZ, Liu YM, Zhang YY, Wang H, Wang C (2010) High prevalence of macrolide resistance in Mycoplasma pneumoniae isolates from adult and adolescent patients with respiratory tract infection in China. Clin Infect Dis 51:189–194CrossRefGoogle Scholar
  6. 6.
    Carabeo RA, Grieshaber SS, Fischer E, Hackstadt T (2002) Chlamydia trachomatis induces remodeling of the actin cytoskeleton during attachment and entry into HeLa cells. Infect Immun 70:3793–3803CrossRefGoogle Scholar
  7. 7.
    Citti C, Nouvel LX, Baranowski E (2010) Phase and antigenic variation in mycoplasmas. Futur Microbiol 5:1073–1085CrossRefGoogle Scholar
  8. 8.
    Duncan DT, Prodduturi N, Zhang B (2010) WebGestalt2: an updated and expanded version of the web-based gene set analysis toolkit. BMC Bioinformatics 11(Suppl 4):P10CrossRefGoogle Scholar
  9. 9.
    Fan T, Lu H, Hu H, Shi L, McClarty GA, Nance DM, Greenberg AH, Zhong G (1998) Inhibition of apoptosis in chlamydia-infected cells: blockade of mitochondrial cytochrome c release and caspase activation. J Exp Med 187:487–496CrossRefGoogle Scholar
  10. 10.
    Fassi Fehri L, Wroblewski H, Blanchard A (2007) Activities of antimicrobial peptides and synergy with enrofloxacin against Mycoplasma pulmonis. Antimicrob Agents Chemother 51:468–474CrossRefGoogle Scholar
  11. 11.
    Goossens H (2009) Antibiotic consumption and link to resistance. Clin Microbiol Infect 15(Suppl 3):12–15CrossRefGoogle Scholar
  12. 12.
    Yount NY, Yeaman MR (2012) Emerging themes and therapeutic prospects for anti-infective peptides. Annu Rev Pharmacol Toxicol 52:337–360CrossRefGoogle Scholar
  13. 13.
    Hancock RE, Sahl HG (2006) Antimicrobial and host-defense peptides as new anti-infective therapeutic strategies. Nat Biotechnol 24:1551–1557CrossRefGoogle Scholar
  14. 14.
    Raulston JE (1995) Chlamydial envelope components and pathogen-host cell interactions. Mol Microbiol 15:607–616CrossRefGoogle Scholar
  15. 15.
    Hayakawa K, Marchaim D, Martin ET, Tiwari N, Yousuf A, Sunkara B, Pulluru H, Kotra H, Hasan A, Bheemreddy S, Sheth P, Lee DW, Kamatam S, Bathina P, Nanjireddy P, Chalana IK, Patel S, Kumar S, Vahia A, Ku K, Yee V, Swan J, Pogue JM, Lephart PR, Rybak MJ, Kaye KS (2012) Comparison of the clinical characteristics and outcomes associated with vancomycin-resistant Enterococcus faecalis and vancomycin-resistant E. faecium bacteremia. Antimicrob Agents Chemother 56:2452–2458CrossRefGoogle Scholar
  16. 16.
    Huang GT, Zhang HB, Kim D, Liu L, Ganz T (2002) A model for antimicrobial gene therapy: demonstration of human beta-defensin 2 antimicrobial activities in vivo. Hum Gene Ther 13:2017–2025CrossRefGoogle Scholar
  17. 17.
    Ison CA (2012) Antimicrobial resistance in sexually transmitted infections in the developed world: implications for rational treatment. Curr Opin Infect Dis 25:73–78CrossRefGoogle Scholar
  18. 18.
    Kozlov SA, Vassilevski AA, Feofanov AV, Surovoy AY, Karpunin DV, Grishin EV (2006) Latarcins, antimicrobial and cytolytic peptides from the venom of the spider Lachesana tarabaevi (Zodariidae) that exemplify biomolecular diversity. J Biol Chem 281:20983–20992CrossRefGoogle Scholar
  19. 19.
    Kuhn-Nentwig L, Stöcklin R, Nentwig W (2011) Venom composition and strategies in spiders: is everything possible? Adv Insect Physiol 40:1–86CrossRefGoogle Scholar
  20. 20.
    Lazarev VN, Parfenova TM, Gularyan SK, Misyurina OY, Akopian TA, Govorun VM (2002) Induced expression of melittin, an antimicrobial peptide, inhibits infection by Chlamydia trachomatis and Mycoplasma hominis in a HeLa cell line. Int J Antimicrob Agents 9:133–137CrossRefGoogle Scholar
  21. 21.
    Lazarev VN, Polina NF, Shkarupeta MM, Kostrjukova ES, Vassilevski AA, Kozlov SA, Grishin EV, Govorun VM (2011) Spider venom peptides for gene therapy of Chlamydia infection. Antimicrob Agents Chemother 55:5367–5369CrossRefGoogle Scholar
  22. 22.
    Lazarev VN, Shkarupeta MM, Titova GA, Kostrjukova ES, Akopian TA, Govorun VM (2005) Effect of induced expression of an antimicrobial peptide melittin on Chlamydia trachomatis and Mycoplasma hominis infections in vivo. Biochem Biophys Res Commun 338:946–950CrossRefGoogle Scholar
  23. 23.
    Lazarev VN, Stipkovits L, Biro J, Miklodi D, Shkarupeta MM, Titova GA, Akopian TA, Govorun VM (2004) Induced expression of the antimicrobial peptide melittin inhibits an experimental infection by Mycoplasma gallisepticum in chickens. Microbes Infect 6:536–541CrossRefGoogle Scholar
  24. 24.
    Liang S (2008) Proteome and peptidome profiling of spider venoms. Expert Rev Proteomics 5:731–746CrossRefGoogle Scholar
  25. 25.
    Morrison RP (2003) New insights into a persistent problem—chlamydial infections. J Clin Invest 111:1647–1649Google Scholar
  26. 26.
    Raghuraman H, Chattopadhyay A (2007) Melittin: a membrane-active peptide with diverse functions. Biosci Rep 27:189–223CrossRefGoogle Scholar
  27. 27.
    Senn L, Hammerschlag MR, Greub G (2005) Therapeutic approaches to Chlamydia infections. Expert Opin Pharmacother 6:2281–2290CrossRefGoogle Scholar
  28. 28.
    Vassilevski AA, Kozlov SA, Grishin EV (2009) Molecular diversity of spider venom. Biochemistry (Mosc) 74:1505–1534CrossRefGoogle Scholar
  29. 29.
    Vassilevski AA, Kozlov SA, Samsonova OV, Egorova NS, Karpunin DV, Pluzhnikov KA, Feofanov AV, Grishin EV (2008) Cyto-insectotoxins, a novel class of cytolytic and insecticidal peptides from spider venom. Biochem J 411:687–696CrossRefGoogle Scholar
  30. 30.
    Vorontsova OV, Egorova NS, Arseniev AS, Feofanov AV (2011) Haemolytic and cytotoxic action of latarcin Ltc2a. Biochimie 93:227–241CrossRefGoogle Scholar
  31. 31.
    Yasin B, Harwig SL, Lehrer RI, Wagar EA (1996) Susceptibility of Chlamydia trachomatis to protegrins and defensins. Infect Immun 64:709–713Google Scholar

Copyright information

© Springer Science + Business Media, LLC 2012

Authors and Affiliations

  • Nadezhda F. Polina
    • 1
  • Marina M. Shkarupeta
    • 1
  • Anna S. Popenko
    • 1
  • Alexander A. Vassilevski
    • 2
  • Sergey A. Kozlov
    • 2
  • Eugene V. Grishin
    • 2
  • Vassili N. Lazarev
    • 1
    • 3
  • Vadim M. Govorun
    • 1
    • 2
    • 3
  1. 1.Research Institute for Physico-Chemical Medicine of the Federal Medical-Biological Agency of Russian FederationMoscowRussia
  2. 2.Shemyakin-Ovchinnikov Institute of Bioorganic ChemistryRussian Academy of SciencesMoscowRussia
  3. 3.National Research Centre “Kurchatov Institute”MoscowRussia

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