Skip to main content
SpringerLink
Log in

Development of anti-acanthamoebic approaches

  • Original Article
  • Published:
International Microbiology Aims and scope Submit manuscript

Abstract

Acanthamoeba keratitis is a sight-endangering eye infection, and causative organism Acanthamoeba presents a significant concern to public health, given escalation of contact lens wearers. Contemporary therapy is burdensome, necessitating prompt diagnosis and aggressive treatment. None of the contact lens disinfectants (local and international) can eradicate Acanthamoeba effectively. Using a range of compounds targeting cellulose, ion channels, and biochemical pathways, we employed bioassay-guided testing to determine their anti-amoebic effects. The results indicated that acarbose, indaziflam, terbuthylazine, glimepiride, inositol, vildagliptin and repaglinide showed anti-amoebic effects. Compounds showed minimal toxicity on human cells. Therefore, effects of the evaluated compounds after conjugation with nanoparticles should certainly be the subject of future studies and will likely lead to promising leads for potential applications.

Graphical abstract

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Data availability

Data sharing is not applicable to this article as no datasets were generated or analysed during the current study.

References

  • 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. Contact Lens Anterio 39(3):239–243

    Article  Google Scholar 

  • Aksozek A, McClellan K, Howard K, Niederkorn JY, Alizadeh H (2002) Resistance of Acanthamoeba castellanii cysts to physical, chemical, and radiological conditions. J Parasitol 88(3):621–623

    Article  CAS  Google Scholar 

  • Anwar A, Khan NA, Siddiqui R (2018a) Combating Acanthamoeba spp. cysts: what are the options? Parasit Vectors 11(1):1–6

    Article  Google Scholar 

  • Anwar A, Siddiqui R, Shah MR, Khan NA (2018b) Gold nanoparticle-conjugated cinnamic acid exhibits antiacanthamoebic and antibacterial properties. Antimicrob Agents Chemother 62(9):e00630–e00618

    Article  CAS  Google Scholar 

  • Anwar A, Soomaroo A, Anwar A, Siddiqui R, Khan NA (2020) Metformin-coated silver nanoparticles exhibit anti-acanthamoebic activities against both trophozoite and cyst stages. Exp Parasitol 215:107915

    Article  CAS  Google Scholar 

  • Dudley R, Alsam S, Khan NA (2007) Cellulose biosynthesis pathway is a potential target in the improved treatment of Acanthamoeba keratitis. Appl Microbiol Biotechnol 75(1):133–140

    Article  CAS  Google Scholar 

  • Dudley R, Jarroll EL, Khan NA (2009) Carbohydrate analysis of Acanthamoeba castellanii. Exp Parasitol 122(4):338–343

    Article  CAS  Google Scholar 

  • Hendiger EB, Padzik M, Żochowska A, Baltaza W, Olędzka G, Zyskowska D, Bluszcz J, Jarzynka S, Chomicz L, Grodzik M, Hendiger J (2020) Tannic acid-modified silver nanoparticles enhance the anti-Acanthamoeba activity of three multipurpose contact lens solutions without increasing their cytotoxicity. Parasit Vectors 13(1):1–8

    Article  Google Scholar 

  • Hiti K, Walochnik J, Haller-Schober EM, Faschinger C, Aspöck H (2002) Viability of Acanthamoeba after exposure to a multipurpose disinfecting contact lens solution and two hydrogen peroxide systems. Br J Ophthalmol 86(2):144–146

    Article  CAS  Google Scholar 

  • Kolar SSN, Manarang JC, Burns AR, Miller WL, McDermott AM, Bergmanson JP (2015) Contact lens care solution killing efficacy against Acanthamoeba castellanii by in vitro testing and live-imaging. Contact Lens Anterio 38(6):442–450

    Article  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • Moon EK, Park HR, Quan FS, Kong HH (2016) Efficacy of Korean multipurpose contact lens disinfecting solutions against Acanthamoeba castellanii. Korean J Parasitol 54(6):697–702

    Article  CAS  Google Scholar 

  • National Center for Biotechnology Information 2020a. PubChem Compound Summary for CID 4091, Metformin. Available online: https://pubchem.ncbi.nlm.nih.gov/compound/Metformin. Accessed Aug. 2, 2020

  • National Center for Biotechnology Information 2020b. PubChem Compound Summary for CID 91739, Quinclorac. Available online: https://pubchem.ncbi.nlm.nih.gov/compound/Quinclorac. Accessed Aug. 2, 2020

  • National Center for Biotechnology Information 2020c. PubChem Compound Summary for CID 44146693, Indaziflam. Available online: https://pubchem.ncbi.nlm.nih.gov/compound/Indaziflam. Accessed Aug. 2, 2020

  • National Center for Biotechnology Information 2020d. PubChem Compound Summary for CID 892, Inositol. Available online: https://pubchem.ncbi.nlm.nih.gov/compound/Inositol. Accessed Aug. 2, 2020

  • National Center for Biotechnology Information 2020e. PubChem Compound Summary for CID 6918537, Vildagliptin. Available online: https://pubchem.ncbi.nlm.nih.gov/compound/Galvus. Accessed Aug. 2, 2020

  • National Center for Biotechnology Information 2020f. PubChem Compound Summary for CID 440950, Cellulase. Available online: https://pubchem.ncbi.nlm.nih.gov/compound/Cellulase. Accessed Aug. 2, 2020

  • National Center for Biotechnology Information 2020g. PubChem Compound Summary for CID 5311309, Nateglinide. Available online: https://pubchem.ncbi.nlm.nih.gov/compound/Nateglinide. Accessed Aug. 2, 2020

  • National Center for Biotechnology Information 2020h. PubChem Compound Summary for CID 3031, 2,6-Dichlorobenzonitrile. Available online: https://pubchem.ncbi.nlm.nih.gov/compound/2_6-Dichlorobenzonitrile. Accessed Aug. 2, 2020

  • National Center for Biotechnology Information 2020i. PubChem Compound Summary for CID 444539, Cinnamic acid. Available online: https://pubchem.ncbi.nlm.nih.gov/compound/Cinnamic-acid. Accessed Aug. 2, 2020

  • National Center for Biotechnology Information, 2020j. PubChem Compound Summary for CID 22206, Terbuthylazine. Available online: https://pubchem.ncbi.nlm.nih.gov/compound/Terbuthylazine. Accessed Aug. 2, 2020

  • National Center for Biotechnology Information 2020k. PubChem Compound Summary for CID 41774, Acarbose. Available online: https://pubchem.ncbi.nlm.nih.gov/compound/Acarbose. Accessed Aug. 2, 2020

  • National Center for Biotechnology Information 2020l. PubChem Compound Summary for CID 3476, Glimepiride. Available online: https://pubchem.ncbi.nlm.nih.gov/compound/Glimepiride. Accessed Aug. 2, 2020

  • National Center for Biotechnology Information 2020m. PubChem Compound Summary for CID 180098, Thaxtomin A. Available online: https://pubchem.ncbi.nlm.nih.gov/compound/Thaxtomin-A. Accessed Aug. 2, 2020

  • National Center for Biotechnology Information 2020n. PubChem Compound Summary for CID 65981, Repaglinide. Available online: https://pubchem.ncbi.nlm.nih.gov/compound/Repaglinide. Accessed Aug. 2, 2020

  • Padzik M, Chomicz L, Szaflik JP, Chruścikowska A, Perkowski K, Szaflik J (2014) In vitro effects of selected contact lens care solutions on Acanthamoeba castellanii strains in Poland. Exp Parasitol 145:S98–S101

    Article  CAS  Google Scholar 

  • Padzik M, Hendiger EB, Żochowska A, Szczepaniak J, Baltaza W, Pietruczuk-Padzik A, Olędzka G, Chomicz L (2019) Evaluation of in vitro effect of selected contact lens solutions conjugated with nanoparticles in terms of preventive approach to public health risk generated by Acanthamoeba strains. Ann Agric Environ Med 26(1):198–202

    Article  CAS  Google Scholar 

  • Pérez-Santonja JJ, Kilvington S, Hughes R, Tufail A, Matheson M, Dart JK (2003) Persistently culture positive Acanthamoeba keratitis: in vivo resistance and in vitro sensitivity. Ophthalmology 110(8):1593–1600

    Article  Google Scholar 

  • Seal DV, Kirkness CM, Bennett HGB, Peterson M, Keratitis Study Group (1999) Population-based cohort study of microbial keratitis in Scotland: incidence and features. Cont Lens Anterior Eye 22(2):49–57

    Article  CAS  Google Scholar 

  • Siddiqui R, Khan NA (2012) Biology and pathogenesis of Acanthamoeba. Parasit Vectors 5(1):6

    Article  Google Scholar 

  • Siddiqui R, Aqeel Y, Khan NA (2016) The development of drugs against Acanthamoeba infections. Antimicrob Agents Chemother 60(11):6441–6450

    Article  CAS  Google Scholar 

  • Siddiqui R, Ong TYY, Jung SY, Khan NA (2017a) Acanthamoeba castellanii interactions with Streptococcus pneumoniae and Streptococcus pyogenes. Exp Parasitol 183:128–132

    Article  CAS  Google Scholar 

  • Siddiqui R, Jeyamogan S, Ali SM, Abbas F, Sagathevan KA, Khan NA (2017b) Crocodiles and Alligators: Antiamoebic and Antitumor Compounds of Crocodiles. Exp Parasitol 183:194–200

    Article  CAS  Google Scholar 

  • Siddiqui R, Roberts SK, Ong TYY, Mungroo MR, Anwar A, Khan NA (2019) Novel insights into the potential role of ion transport in sensory perception in Acanthamoeba. Parasite vector 12(1):538

    Article  Google Scholar 

  • Stehr-Green JK, Bailey TM, Visvesvara GS (1989) The epidemiology of Acanthamoeba keratitis in the United States. Am J Ophthalmol 107(4):331–336

    Article  CAS  Google Scholar 

  • Tu EY, Joslin CE (2010) Recent outbreaks of atypical contact lens-related keratitis: what have we learned? Am J Ophthalmol 150(5):602–608

    Article  Google Scholar 

  • Üstüntürk M, Zeybek Z (2014) Amoebicidal efficacy of a novel multi-purpose disinfecting solution: first findings. Exp Parasitol 145:S93–S97

    Article  Google Scholar 

  • Visvesvara GS, Moura H, Schuster FL (2007) Pathogenic & free-living amoebae: Acanthamoeba, Balamuthia, Naegleria & Sappinia. FEMS Immunol Med Microbiol 50(1):1–26

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We are grateful to University of Sharjah, UAE, for supporting this work.

Funding

This research was funded by the Fundamental Research Grant Scheme No. FRGS/1/2018/SKK08/S4UC/01/1, Sunway University, Malaysia.

Author information

Authors and Affiliations

  1. Department of Biological Sciences, School of Medical and Life Sciences, Sunway University, Bandar Sunway, Selangor, Malaysia

    Mohammad Ridwane Mungroo & Tommy Tong

  2. Department of Clinical Sciences, College of Medicine, University of Sharjah, University City, Sharjah, United Arab Emirates

    Naveed Ahmed Khan

  3. Centre for Medical Laboratory Technology Studies, Faculty of Health Sciences, Universiti Teknologi MARA, Puncak Alam Campus, Shah Alam, Selangor, Malaysia

    Tengku Shahrul Anuar

  4. Centre for Discovery Brain Science, Biomedical Sciences, Edinburgh Medical School, University of Edinburgh, Edinburgh, Scotland, UK

    Sutherland K. Maciver

  5. College of Arts and Sciences, American University of Sharjah, University City, Sharjah, United Arab Emirates

    Ruqaiyyah Siddiqui

Authors
  1. Mohammad Ridwane Mungroo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tommy Tong
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Naveed Ahmed Khan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Tengku Shahrul Anuar
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Sutherland K. Maciver
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ruqaiyyah Siddiqui
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

RS and NAK conceived the study and obtained funding for the study amid discussion with TT, SKM and TSA. MR conducted all investigations and data analysis under the supervision of TT, RS and NAK. MR, RS and NAK contributed to the writing of the manuscript. All authors approved the final manuscript.

Corresponding authors

Correspondence to Tommy Tong or Naveed Ahmed Khan.

Ethics declarations

Ethics approval and consent to participate

This article does not contain any studies with human participants. This article does not contain any studies involving animals.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Significance and impact of the study

During the past few decades Acanthamoeba have gained significant attention as important human pathogens producing vision-threatening keratitis and a rare but fatal encephalitis known as granulomatous amoebic encephalitis. In the present study, we tested several compounds targeting cellulose, ion channels and biochemical pathways against A. castellanii. Selected compounds exhibited anti-amoebic effects. Conversely, the compounds caused none or limited host cell damage. These findings are very encouraging and could provide a basis for further studies using nanomedicine in the development of effective preventative and/or therapeutic strategies; however, detailed underlying molecular mechanisms need to be explored to realize these expectations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mungroo, M.R., Tong, T., Khan, N.A. et al. Development of anti-acanthamoebic approaches. Int Microbiol 24, 363–371 (2021). https://doi.org/10.1007/s10123-021-00171-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10123-021-00171-3

Keywords

Search

Navigation