Journal of Microbiology and Biotechnology
The Korean Society for Microbiology and Biotechnology publishes the Journal of Microbiology and Biotechnology.

2019 ; Vol.29-5: 713~720

AuthorAyaz Anwar, Ruqaiyyah Siddiqui, Muhammad Raza Shah, Naveed Ahmed Khan
Place of dutyDepartment of Biological Sciences, School of Science and Technology, Sunway University, Malaysia.
TitleAntidiabetic Drugs and Their Nanoconjugates Repurposed as Novel Antimicrobial Agents against Acanthamoeba castellanii
PublicationInfo J. Microbiol. Biotechnol.2019 ; Vol.29-5
AbstractAcanthamoeba 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.
Full-Text
Key_wordAcanthamoeba, antiparasitic, antidiabetic drugs, nanoparticles
References
  1. Seal D V. 2 0 0. 3Acanthamoeba keratitis update-incidence, molecular epidemiology and new drugs for treatment. Eye 17: 893-905.
    Pubmed CrossRef
  2. Marciano-Cabral F, Cabral G. 2003. Acanthamoeba spp. as agents of disease in humans. Clin. Microbiol. Rev. 16: 273-307.
    Pubmed CrossRef Pubmed Central
  3. Illingworth CD, Cook SD, Karabatsas CH, Easty DL. 1995. Acanthamoeba keratitis: risk factors and outcome. Br. J. Ophthalmol. 79: 1078-1082.
    Pubmed CrossRef Pubmed Central
  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.
    Pubmed CrossRef
  5. Khan N A. 2 0 0. 6Acanthamoeba: biology and increasing importance in human health. FEMS Microbiol. Rev. 30: 564-595.
    Pubmed CrossRef
  6. Lorenzo-Morales J, Khan NA, Walochnik J. 2015. An update on Acanthamoeba keratitis: diagnosis, pathogenesis and treatment. Parasite 2015: 22: 10.
    Pubmed CrossRef Pubmed Central
  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.
    Pubmed CrossRef Pubmed Central
  8. Ortillés Á, Belloc J, Rubio E, Fernández MT, Benito M, Cristóbal JÁ, et al. 2017. In-vitro development of an effective treatment for Acanthamoeba keratitis. Int. J. Antimicrob. Agents 50: 325-333.
    Pubmed CrossRef
  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.
    Pubmed CrossRef
  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.
    Pubmed CrossRef
  11. Imran M, Muazzam AG, Habib A, Matin A. 2016. Synthesis, characterization and amoebicidal potential of locally synthesized TiO2 nanoparticles against pathogenic Acanthamoeba trophozoites in vitro. J. Photochem. Photobiol. B: Biol. 159: 125-132.
    Pubmed CrossRef
  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.
    CrossRef
  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.
    Pubmed CrossRef Pubmed Central
  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.
    Pubmed CrossRef
  15. Anwar A, Khan NA, Siddiqui R, 2018. Combating Acanthamoeba spp. cysts: what are the options? Parasit. Vectors 11: 26.
    Pubmed CrossRef Pubmed Central
  16. Dudley R, Jarroll EL, Khan NA. 2009. Carbohydrate analysis of Acanthamoeba castellanii. Exp. Parasitol. 122: 338-343.
    Pubmed CrossRef
  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.
    Pubmed CrossRef Pubmed Central
  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.
    Pubmed CrossRef
  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.
    Pubmed CrossRef Pubmed Central
  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.
    Pubmed CrossRef
  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.
    Pubmed CrossRef
  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.
    Pubmed CrossRef Pubmed Central
  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.
    Pubmed CrossRef Pubmed Central
  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.
    Pubmed CrossRef Pubmed Central
  25. Debnath A, Tunac JB, Silva-Olivares A, Galindo-Gómez S, Shibayama M, McKerrow JH. 2014. In vitro efficacy of corifungin against Acanthamoeba castellanii trophozoites and cysts. Antimicrob. Agents Chemother. 58: 1523-1528.
    Pubmed CrossRef Pubmed Central
  26. Campbell RK. 1998. Glimepiride: role of a new sulfonylurea in the treatment of type 2 diabetes mellitus. Ann. Pharmacother. 32: 1044-1052.
    Pubmed CrossRef
  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.
    CrossRef
  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.
    CrossRef
  29. Ahrén 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.
    Pubmed CrossRef
  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.
    Pubmed CrossRef Pubmed Central
  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.
    CrossRef
  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.
    Pubmed CrossRef
  33. Malaisse WJ. 1999. Repaglinide, a new oral antidiabetic agent: a review of recent preclinical studies. Eur. J. Clin. Invest. 29: 21-29.
    Pubmed CrossRef
  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.
    Pubmed CrossRef Pubmed Central
  35. Baig AM, Zuberi H, Khan NA. 2014. Recommendations for the management of Acanthamoeba keratitis. J. Med. Microbiol. 63: 770-771.
    Pubmed CrossRef
  36. Kumari A, Y adav S K, Y adav S C. 2 0 10. Biodegradable polymeric nanoparticles based drug delivery systems. Colloids Surf. B: Biointerfaces 75: 1-8.
    Pubmed CrossRef
  37. De las Heras Alarcón C, Pennadam S, Alexander C. 2005. Stimuli responsive polymers for biomedical applications. Chem. Soc. Rev. 34: 276-285.
    Pubmed CrossRef
  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.
    Pubmed CrossRef



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