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Antidiabetic Drugs and Their Nanoconjugates Repurposed as Novel Antimicrobial Agents against Acanthamoeba castellanii

  • Anwar, Ayaz (Department of Biological Sciences, School of Science and Technology, Sunway University) ;
  • Siddiqui, Ruqaiyyah (Department of Biological Sciences, School of Science and Technology, Sunway University) ;
  • Shah, Muhammad Raza (HEJ Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi) ;
  • Khan, Naveed Ahmed (Department of Biological Sciences, School of Science and Technology, Sunway University)
  • Received : 2019.03.06
  • Accepted : 2019.04.13
  • Published : 2019.05.28

Abstract

Acanthamoeba castellanii belonging to the T4 genotype may cause a fatal brain infection known as granulomatous amoebic encephalitis, and the vision-threatening eye infection Acanthamoeba keratitis. The aim of this study was to evaluate the antiamoebic effects of three clinically available antidiabetic drugs, Glimepiride, Vildagliptin and Repaglinide, against A. castellanii belonging to the T4 genotype. Furthermore, we attempted to conjugate these drugs with silver nanoparticles (AgNPs) to enhance their antiamoebic effects. Amoebicidal, encystation, excystation, and host cell cytotoxicity assays were performed to unravel any antiacanthamoebic effects. Vildagliptin conjugated silver nanoparticles (Vgt-AgNPs) characterized by spectroscopic techniques and atomic force microscopy were synthesized. All three drugs showed antiamoebic effects against A. castellanii and significantly blocked the encystation. These drugs also showed significant cysticidal effects and reduced host cell cytotoxicity caused by A. castellanii. Moreover, Vildagliptin-coated silver nanoparticles were successfully synthesized and are shown to enhance its antiacanthamoebic potency at significantly reduced concentration. The repurposed application of the tested antidiabetic drugs and their nanoparticles against free-living amoeba such as Acanthamoeba castellanii described here is a novel outcome that holds tremendous potential for future applications against devastating infection.

Keywords

References

  1. Seal DV. 2003. Acanthamoeba keratitis update-incidence, molecular epidemiology and new drugs for treatment. Eye 17: 893-905. https://doi.org/10.1038/sj.eye.6700563
  2. Marciano-Cabral F, Cabral G. 2003. Acanthamoeba spp. as agents of disease in humans. Clin. Microbiol. Rev. 16: 273-307. https://doi.org/10.1128/CMR.16.2.273-307.2003
  3. Illingworth CD, Cook SD, Karabatsas CH, Easty DL. 1995. Acanthamoeba keratitis: risk factors and outcome. Br. J. Ophthalmol. 79: 1078-1082. https://doi.org/10.1136/bjo.79.12.1078
  4. Visvesvara GS, Moura H, Schuster FL. 2007. Pathogenic and opportunistic free-living amoebae: Acanthamoeba spp., Balamuthia mandrillaris, Naegleria fowleri, and Sappinia diploidea. FEMS Immun. Med. Microbiol. 50: 1-26. https://doi.org/10.1111/j.1574-695X.2007.00232.x
  5. Khan NA. 2006. Acanthamoeba: biology and increasing importance in human health. FEMS Microbiol. Rev. 30: 564-595. https://doi.org/10.1111/j.1574-6976.2006.00023.x
  6. Lorenzo-Morales J, Khan NA, Walochnik J. 2015. An update on Acanthamoeba keratitis: diagnosis, pathogenesis and treatment. Parasite 2015: 22: 10. https://doi.org/10.1051/parasite/2015010
  7. Coulon C, Collignon A, McDonnell G, Thomas V. 2010. Resistance of Acanthamoeba cysts to disinfection treatments used in health care settings. J. Clin. Microbiol. 48: 2689-2697. https://doi.org/10.1128/JCM.00309-10
  8. Ortilles A, Belloc J, Rubio E, Fernandez MT, Benito M, Cristobal JA, et al. 2017. In-vitro development of an effective treatment for Acanthamoeba keratitis. Int. J. Antimicrob. Agents 50: 325-333. https://doi.org/10.1016/j.ijantimicag.2017.03.033
  9. Huh AJ, Kwon YJ. 2011. "Nanoantibiotics": a new paradigm for treating infectious diseases using nanomaterials in the antibiotics resistant era. J. Control. Release 156: 128-145. https://doi.org/10.1016/j.jconrel.2011.07.002
  10. Borase HP, Patil CD, Sauter IP, Rott MB, Patil SV. 2013. Amoebicidal activity of phytosynthesized silver nanoparticles and their in vitro cytotoxicity to human cells. FEMS Microbiol. Lett. 345: 127-131. https://doi.org/10.1111/1574-6968.12195
  11. Imran M, Muazzam AG, Habib A, Matin A. 2016. Synthesis, characterization and amoebicidal potential of locally synthesized $TiO_2$ nanoparticles against pathogenic Acanthamoeba trophozoites in vitro. J. Photochem. Photobiol. B: Biol. 159: 125-132. https://doi.org/10.1016/j.jphotobiol.2016.03.014
  12. Willcox MD, Hume EB, Vijay AK, Petcavich R. 2010. Ability of silver-impregnated contact lenses to control microbial growth and colonisation. J. Optometry 3: 143-148. https://doi.org/10.1016/S1888-4296(10)70020-0
  13. Aqeel Y, Siddiqui R, Anwar A, Shah MR, Khan NA. 2016. Gold nanoparticle conjugation enhances the antiacanthamoebic effects of chlorhexidine. Antimicrob. Agents Chemother. 60:1283-1288. https://doi.org/10.1128/AAC.01123-15
  14. Anwar A, Siddiqui R, Shah MR, Khan NA. 2019. Gold nanoparticles conjugation enhances antiacanthamoebic properties of nystatin, fluconazole and amphotericin B. J. Microbiol. Biotechnol. 29: 171-177. https://doi.org/10.4014/jmb.1805.05028
  15. Anwar A, Khan NA, Siddiqui R, 2018. Combating Acanthamoeba spp. cysts: what are the options? Parasit. Vectors 11: 26. https://doi.org/10.1186/s13071-017-2572-z
  16. Dudley R, Jarroll EL, Khan NA. 2009. Carbohydrate analysis of Acanthamoeba castellanii. Exp. Parasitol. 122: 338-343. https://doi.org/10.1016/j.exppara.2009.04.009
  17. Lorenzo-Morales J, Kliescikova J, Martinez-Carretero E, De Pablos LM, Profotova B, Nohynkova E, et al. 2008. Glycogen phosphorylase in Acanthamoeba spp.: determining the role of the enzyme during the encystment process using RNA interference. Eukaryot. Cell. 7: 509-517. https://doi.org/10.1128/EC.00316-07
  18. Abjani F, Khan NA, Yousuf FA, Siddiqui R. 2016. Targeting cyst wall is an effective strategy in improving the efficacy of marketed contact lens disinfecting solutions against Acanthamoeba castellanii cysts. Cont. Lens Anterior Eye 39: 239-243. https://doi.org/10.1016/j.clae.2015.11.004
  19. Sissons J, Alsam S, Stins M, Rivas AO, Morales JL, Faull J, et al. 2006. Use of in vitro assays to determine effects of human serum on biological characteristics of Acanthamoeba castellanii. J. Clin. Microbiol. 44: 2595-2600. https://doi.org/10.1128/JCM.00144-06
  20. Anwar A, Siddiqui R, Hussain MA, Ahmed D, Shah MR, Khan NA. 2018. Silver nanoparticle conjugation affects antiacanthamoebic activities of amphotericin B, nystatin, and fluconazole. Parasitol. Res. 117: 265-271. https://doi.org/10.1007/s00436-017-5701-x
  21. Lakhundi S, Khan NA, Siddiqui R. 2014. Inefficacy of marketed contact lens disinfection solutions against keratitis-causing Acanthamoeba castellanii belonging to the T4 genotype. Exp. Parasitol. 141: 122-128. https://doi.org/10.1016/j.exppara.2014.03.018
  22. Sissons J, Kim KS, Stins M, Jayasekera S, Alsam S, Khan NA. 2005. Acanthamoeba castellanii induces host cell death via a phosphatidylinositol 3-kinase-dependent mechanism. Infect. Immun. 73: 2704-2708. https://doi.org/10.1128/IAI.73.5.2704-2708.2005
  23. Anwar A, Siddiqui R, Shah MR, Khan NA. 2018. Gold nanoparticle-conjugated cinnamic acid exhibits antiacanthamoebic and antibacterial properties. Antimicrob. Agents Chemother. 62: e00630-18.
  24. Masri A, Anwar A, Ahmed D, Siddiqui R, Shah MR, Khan N. 2018. Silver nanoparticle conjugation enhanced antibacterial efficacy of clinically approved drugs Cephradine and Vildagliptin. Antibiotics 7: 100. https://doi.org/10.3390/antibiotics7040100
  25. Debnath A, Tunac JB, Silva-Olivares A, Galindo-Gomez S, Shibayama M, McKerrow JH. 2014. In vitro efficacy of corifungin against Acanthamoeba castellanii trophozoites and cysts. Antimicrob. Agents Chemother. 58: 1523-1528. https://doi.org/10.1128/AAC.02254-13
  26. Campbell RK. 1998. Glimepiride: role of a new sulfonylurea in the treatment of type 2 diabetes mellitus. Ann. Pharmacother. 32: 1044-1052. https://doi.org/10.1345/aph.17360
  27. Muller G. 2005. The mode of action of the antidiabetic drug glimepiride-beyond insulin secretion. Immunol. Endocr. Metab. Agents Med. Chem. 5: 499-518. https://doi.org/10.2174/156801305774962123
  28. Abd El-Wahed M, El-Megharbel S, El-Sayed M, Zahran Y, Refat M. 2013. Synthesis of several new lanthanide Glimepiride complexes for evaluation of microbial activity. Russ. J. Gen. Chem. 83: 2438-2446. https://doi.org/10.1134/S1070363213120402
  29. Ahren B, Schweizer A, Dejager S, Villhauer EB, Dunning BE, Foley JE. 2011. Mechanisms of action of the dipeptidyl peptidase-4 inhibitor vildagliptin in humans. Diabetes Obes. Metab. 13: 775-783. https://doi.org/10.1111/j.1463-1326.2011.01414.x
  30. Al-Abdullah E, Al-Tuwaijri H, Hassan H, Al-Alshaikh M, Habib E, El-Emam A. 2015. Synthesis, antimicrobial and hypoglycemic activities of novel N-(1-adamantyl) carbothioamide derivatives. Molecules 20: 8125-8143. https://doi.org/10.3390/molecules20058125
  31. Waghulde M, Naik J. 2017. Comparative study of encapsulated vildagliptin microparticles produced by spray drying and solvent evaporation technique. Drying Technol. 35: 1644-1654. https://doi.org/10.1080/07373937.2016.1273230
  32. Baig MMFA, Khan S, Naeem MA, Khan GJ, Ansari MT. 2018. Vildagliptin loaded triangular DNA nanospheres coated with eudragit for oral delivery and better glycemic control in type 2 diabetes mellitus. Biomed. Pharmacother. 97:1250-1258. https://doi.org/10.1016/j.biopha.2017.11.059
  33. Malaisse WJ. 1999. Repaglinide, a new oral antidiabetic agent: a review of recent preclinical studies. Eur. J. Clin. Invest. 29: 21-29. https://doi.org/10.1046/j.1365-2362.1999.00001.x
  34. Baig AM, Iqbal J, Khan NA. 2013. In vitro efficacies of clinically available drugs against growth and viability of an Acanthamoeba castellanii keratitis isolate belonging to the T4 genotype. Antimicrob. Agents Chemother. 57: 3561-3567. https://doi.org/10.1128/AAC.00299-13
  35. Baig AM, Zuberi H, Khan NA. 2014. Recommendations for the management of Acanthamoeba keratitis. J. Med. Microbiol. 63: 770-771. https://doi.org/10.1099/jmm.0.069237-0
  36. Kumari A, Yadav SK, Yadav SC. 2010. Biodegradable polymeric nanoparticles based drug delivery systems. Colloids Surf. B: Biointerfaces 75: 1-8. https://doi.org/10.1016/j.colsurfb.2009.09.001
  37. De las Heras Alarcon C, Pennadam S, Alexander C. 2005. Stimuli responsive polymers for biomedical applications. Chem. Soc. Rev. 34: 276-285. https://doi.org/10.1039/B406727D
  38. Sondi I, Salopek-Sondi B. 2004. Silver nanoparticles as antimicrobial agent: a case study on E. coli as a model for Gram-negative bacteria. J. Colloids Interface Sci. 275: 177-182. https://doi.org/10.1016/j.jcis.2004.02.012

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