A Novel Strategy for Enhance Potentiation of Meglumine anti-moniate against Leishmania major In Vitro
AbstractBackground: We aimed to design a different method of drug delivery for increased transfer of the choice drug (meglumine antimoniate) within the host cells. Therefore, listeriolysin O (LLO), a bacterial product which is a member of pore-forming peptides was used as an enhancer factor with meglumine antimoniate in order to facilitate the transition of the drug across macrophage membrane.Methods: LLO was produced in Isfahan University of Medical Sciences in 2016, by expressing the hlyA gene in Escherichia coli and purified using affinity chromatography. Cytotoxicity of the purified protein was investigated in an in vitro model of macrophage Leishmania infection.Results: LLO was cytotoxic against murine macrophage cells (J774-A1) and amastigote forms of L. major (MRHO/IR/75/ER). It was less toxic to macrophages (CC50=2.56 μg ml-1 ±0.09) than to the parasites (IC50=1.72 μg ml-1 ±0.07). Moreover, non-cytotoxic concentration of LLO (0.006 ug ml-1) potentiated the cytotoxicity induced by low dose concentration of meglumine antimoniate. Very little dose of meglumine antimoniate was needed when combined with the LLO (IC50=12.63 μg ml-1 ±0.13) in comparison with the cytotoxicity induced when the drug is used alone (IC50=46.17 μg ml-1 ±0.28).Conclusion: The combination of pore-forming proteins with anti-leishmanial agents could increase the advantage of anti-leishmanial drugs. Since lower concentrations of anti-leishmanial drugs can reduce undesirable side effects of chemotherapy trials carried out in animal models and then in humans with this system.
Murray H W, Berman J D, Davies C R, Saravia N G, Advances in leishmaniasis. Lancet, 2005. 366(9496): p. 1561-77.
Hatam G, Rezanezhad H, Motazedian M, Sarkari B, In vitro infectivity of Leishmania major isolated from patients with different clinical forms of cutaneous leishmaniasis and its association with parasite zymodems. Iran J parasitol, 2009. 4(3): p. 52-60.
Mahmoudvand H, Shakibaie M, Tavakoli R, Jahanbakhsh S, Sharifi I, In Vitro Study of Leishmanicidal Activity of Biogenic Selenium Nanoparticles against Iranian Isolate of Sensitive and Glucantime-Resistant Leishmania tropica. Iran J parasitol, 2014. o9(4): p. 452.
Rottini M M, Amaral A C F, Ferreira J L P, de Andrade Silva J R, Noemi Nosomi, de Souza C d S F, d'Escoffier L N, Almeida-Souza F, de Jesus Hardoim D, da Costa S C G, In vitro evaluation of (−) α-bisabolol as a promising agent against Leishmania amazonensis. Exp Parasitol., 2015. 148: p. 66-72.
Guerin P J, Olliaro P, Sundar S, Boelaert M, Croft S L, Desjeux P, Wasunna M K, Bryceson A D, Visceral leishmaniasis: current status of control, diagnosis, and treatment, and a proposed research and development agenda. Lancet Infect Dis, 2002. 2(8): p. 494-501.
Davies C R, Kaye P, Croft S L, Sundar S, Leishmaniasis: new approaches to disease control. BMJ, 2003. 326(7385): p. 377-82.
Riabi T R, Sharifi I, Mohammadi A M, Khamesipour A, Parizi M H, Evaluation of a possible synergistic effect of meglumine antimoniate with paromomycin, miltefosine or allopurinol on in vitro susceptibility of Leishmania tropica resistant isolate. Iran J parasitol, 2013. 8(3): p. 396.
Yasinzai M, Khan M, Nadhman A, Shahnaz G, Drug resistance in leishmaniasis: current drug-delivery systems and future perspectives. Future Med Chem, 2013. 5(15): p. 1877-88.
Romero E L,Morilla M J, Drug delivery systems against leishmaniasis? Still an open question. Expert Opin Drug Deliv, 2008. 5(7): p. 805-23.
Soletti R C, de Faria G P, Vernal J, Terenzi H, Anderluh G, Borges H L, Moura-Neto V, Gabilan N H, Potentiation of anticancer-drug cytotoxicity by sea anemone pore-forming proteins in human glioblastoma cells. Anti-cancer drugs, 2008. 19(5): p. 517-525.
Belting M, Sandgren S, Wittrup A, Nuclear delivery of macromolecules: barriers and carriers. Adv Drug Deliv Rev, 2005. 57(4): p. 505-27.
Majd S, Yusko E C, Billeh Y N, Macrae M X, Yang J, Mayer M, Applications of biological pores in nanomedicine, sensing, and nanoelectronics. Curr Opin Biotechnol, 2010. 21(4): p. 439-76.
Kim N H, Provoda C, Lee K D, Design and characterization of novel recombinant listeriolysin O-protamine fusion proteins for enhanced gene delivery. Mol Pharm, 2015. 12(2): p. 342-50.
Churchill R L, Lee H, Hall J C, Rapid purification of recombinant listeriolysin O (LLO) from Escherichia coli. J Ind Microbiol Biotechnol, 2005. 32(8): p. 355-63.
Zamani M, Berenjian A, Hemmati S, Nezafat N, Ghoshoon M B, Dabbagh F, Mohkam M, Ghasemi Y, Cloning, Expression, and Purification of a Synthetic Human Growth Hormone in Escherichia coli Using Response Surface Methodology. Molecular biotechnology, 2015. 57(3): p. 241-250.
Gupta S, Sundar S, Goyal N, Use of Leishmania donovani field isolates expressing the luciferase reporter gene in in vitro drug screening. Antimicrobial agents and chemotherapy, 2005. 49(9): p. 3776-3783.
Celia C, Trapasso E, Locatelli M, Navarra M, Ventura C, Wolfram J, Carafa M, Morittu V, Britti D, Di Marzio L, Anticancer activity of liposomal bergamot essential oil (BEO) on human neuroblastoma cells. Colloids and surfaces. B, Biointerfaces, 2013. 112: p. 548.
Ezatpour B, Saedi Dezaki E, Mahmoudvand H, Azadpour M, Ezzatkhah F, In vitro and in vivo antileishmanial effects of Pistacia khinjuk against Leishmania tropica and Leishmania major. Evidence-Based Complementary and Alternative Medicine, 2015. 2015.
Organization W H, Control of the leishmaniases: report of a meeting of the WHO Expert Commitee on the Control of Leishmaniases, Geneva, 22-26 March 2010. 2010.
Gutiérrez V, Seabra A B, Reguera R M, Khandare J, Calderón M, New approaches from nanomedicine for treating leishmaniasis. Chemical Society Reviews, 2016. 45(1): p. 152-168.
Nicoletti S, Seifert K, Gilbert I H, N-(2-hydroxypropyl) methacrylamide–amphotericin B (HPMA–AmB) copolymer conjugates as antileishmanial agents. International journal of antimicrobial agents, 2009. 33(5): p. 441.
Perez A P, Casasco A, Schilrreff P, Tesoriero M V D, Duempelmann L, Altube M J, Higa L, Morilla M J, Petray P, Romero E L, Enhanced photodynamic leishmanicidal activity of hydrophobic zinc phthalocyanine within archaeolipids containing liposomes. International journal of nanomedicine, 2014. 9: p. 3335.
Barros D, Costa L S, Cordeiro-da-Silva A, Surface functionalization of polymeric nanospheres modulates macrophage activation: relevance in leishmaniasis therapy. Nanomedicine (London, England), 2015. 10(3): p. 387.
Provoda C, Stier E, Lee K, Tumor cell killing enabled by listeriolysin O-liposome-mediated delivery of the protein toxin gelonin. The Journal of biological chemistry, 2003. 278(37): p. 35102.
Frézard F, Demicheli C, Ribeiro R R, Pentavalent antimonials: new perspectives for old drugs. Molecules, 2009. 14(7): p. 2317-2336.
Panchal R, Smart M, Bowser D, Williams D, Petrou S, Pore-forming proteins and their application in biotechnology. Current pharmaceutical biotechnology, 2002. 3(2): p. 99-115.
Lee K, Oh Y, Portnoy D, Swanson J, Delivery of macromolecules into cytosol using liposomes containing hemolysin from Listeria monocytogenes. The Journal of biological chemistry, 1996. 271(13): p. 7249.
Mandal M,Lee K, Listeriolysin O-liposome-mediated cytosolic delivery of macromolecule antigen in vivo: enhancement of antigen-specific cytotoxic T lymphocyte frequency, activity, and tumor protection. Biochim Biophys Acta, 2002. 1563(1-2): p. 7.
Hamon M A, Ribet D, Stavru F, Cossart P, Listeriolysin O: the Swiss army knife of Listeria. Trends Microbiol, 2012. 20(8): p. 360-8.