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Amoebicidal effect of Fluconazole and Verapamil together against trophozoites and cysts of Acanthamoeba castellanii

Yıl 2023, Cilt: 12 Sayı: 2, 104 - 110, 22.06.2023

Mehmet Aykur

https://doi.org/10.46810/tdfd.1259142

Öz

Acanthamoeba species are an important pathogen that causes Acanthamoeba keratitis, which causes a visual loss, and encephalitis, which lead to the central nervous system infection and death. The options available to successfully treat Acanthamoeba infections have limited success. New therapeutic approaches must thus be developed, and especially combination medication therapy may be a successful and an effective strategy. The aim of this study was to assess the combination efficacy of verapamil and fluconazole against Acanthamoeba trophozoites and cysts. The effects of drugs on growth inhibition against Acanthamoeba were tested using amoebicidal assays. The viability of Acanthamoeba was assessed using Trypan blue and hemocytometer counts. The effect of three different concentrations of fluconazole, verapamil and fluconazole + verapamil combination on growth inhibition against Acanthamoeba trophozoites and cysts was significant compared to the control (p<0.05). While Acanthamoeba reduced the viability of 250 µg/ml fluconazole and verapamil on trophozoites to 2.3 x 104 and 3 x 104 numbers, fluconazole + verapamil combination showed 100% growth inhibition on trophozoites. Moreover, the combination of 250 µg/ml fluconazole + verapamil showed up to 90% growth inhibition on cysts. As a result, it was revealed that the combination of fluconazole and verapamil was more effective against the trophozoites and cysts of Acanthamoeba.

Anahtar Kelimeler

Acanthamoeba castellanii Fluconazole Verapamil Combination Amoebicidal effect Growth inhibition

Kaynakça

  • Khan NA. Acanthamoeba: biology and increasing importance in human health. FEMS microbiology reviews. 2006;30(4):564-95.
  • Marciano-Cabral F, Cabral G. Acanthamoeba spp. as agents of disease in humans. Clinical microbiology reviews. 2003;16(2):273-307.
  • De Jonckheere JF. Ecology of Acanthamoeba. Reviews of infectious diseases. 1991;13 Suppl 5:S385-7.
  • de Lacerda AG, Lira M. Acanthamoeba keratitis: a review of biology, pathophysiology and epidemiology. Ophthalmic Physiol Opt. 2021;41(1):116-35.
  • Putaporntip C, Kuamsab N, Nuprasert W, Rojrung R, Pattanawong U, Tia T, et al. Analysis of Acanthamoeba genotypes from public freshwater sources in Thailand reveals a new genotype, T23 Acanthamoeba bangkokensis sp. nov. Scientific reports. 2021;11(1).
  • Visvesvara GS, Moura H, Schuster FL. Pathogenic and opportunistic free-living amoebae: Acanthamoeba spp., Balamuthia mandrillaris, Naegleria fowleri, and Sappinia diploidea. FEMS immunology and medical microbiology. 2007;50(1):1-26.
  • Radford CF, Bacon AS, Dart JK, Minassian DC. Risk factors for acanthamoeba keratitis in contact lens users: a case-control study. Bmj. 1995;310(6994):1567-70.
  • Carnt N, Hoffman JJ, Verma S, Hau S, Radford CF, Minassian DC, et al. Acanthamoeba keratitis: confirmation of the UK outbreak and a prospective case-control study identifying contributing risk factors. British Journal of Ophthalmology. 2018;102(12):1621-8.
  • Nakaminami H, Tanuma K, Enomoto K, Yoshimura Y, Onuki T, Nihonyanagi S, et al. Evaluation of In Vitro Antiamoebic Activity of Antimicrobial Agents Against Clinical Acanthamoeba Isolates. Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics. 2017.
  • Lorenzo-Morales J, Khan NA, Walochnik J. An update on Acanthamoeba keratitis: diagnosis, pathogenesis and treatment. Parasite. 2015;22:10.
  • Varacalli G, Di Zazzo A, Mori T, Dohlman TH, Spelta S, Coassin M, et al. Challenges in Acanthamoeba Keratitis: A Review. Journal of Clinical Medicine. 2021;10(5).
  • Fanselow N, Sirajuddin N, Yin X-T, Huang AJW, Stuart PM. Acanthamoeba Keratitis, Pathology, Diagnosis and Treatment. Pathogens. 2021;10(3).
  • Carrijo-Carvalho LC, Sant'ana VP, Foronda AS, de Freitas D, de Souza Carvalho FR. Therapeutic agents and biocides for ocular infections by free-living amoebae of Acanthamoeba genus. Surv Ophthalmol. 2017;62(2):203-18.
  • McCoy C, Patel S, Thulasi P. Update on the Management of Acanthamoeba Keratitis. Current Ophthalmology Reports. 2022.
  • Kalra SK, Sharma P, Shyam K, Tejan N, Ghoshal U. Acanthamoeba and its pathogenic role in granulomatous amebic encephalitis. Experimental parasitology. 2020;208.
  • Szentmary N, Daas L, Shi L, Laurik KL, Lepper S, Milioti G, et al. Acanthamoeba keratitis - Clinical signs, differential diagnosis and treatment. J Curr Ophthalmol. 2019;31(1):16-23.
  • Liu S, Yue L, Gu W, Li X, Zhang L, Sun S. Synergistic effect of fluconazole and calcium channel blockers against resistant Candida albicans. PloS one. 2016;11(3):e0150859.
  • Spampinato C, Leonardi D. Candida infections, causes, targets, and resistance mechanisms: traditional and alternative antifungal agents. BioMed research international. 2013;2013.
  • Anwar A, Siddiqui R, Hussain MA, Ahmed D, Shah MR, Khan NA. Silver nanoparticle conjugation affects antiacanthamoebic activities of amphotericin B, nystatin, and fluconazole. Parasitology research. 2018;117(1):265-71.
  • Baig AM, Zohaib R, Nuzair W, Saiqa K, Mehdia N. Evidence of human‐like Ca2+ Channels and Effects of Ca2+ Channel blockers in Acanthamoeba castellanii. Chemical biology & drug design. 2018.
  • Rodrigues AA, Pina-Vaz C, Mardh PA, Martinez-de-Oliveira J, Freitas-da-Fonseca A. Inhibition of germ tube formation by Candida albicans by local anesthetics: an effect related to ionic channel blockade. Current microbiology. 2000;40(3):145-8.
  • Baig AM, Khaleeq A, Nazim F. Targeting CNS Related Protist Pathogens: Calcium Ion Dependency in the Brain-Eating Amoebae. ACS Chem Neurosci. 2019.
  • Baig AM. Drug targeting in Acanthamoeba keratitis: rational of using drugs that are already approved for ocular use in non-keratitis indications. Eye (London, England). 2018.
  • Baig AM, Iqbal J, Khan NA. In vitro efficacy of clinically available drugs against growth and viability of Acanthamoeba castellanii keratitis isolate belonging to the T4 genotype. Antimicrobial agents and chemotherapy. 2013:AAC. 00299-13.
  • Yu Q, Ding X, Zhang B, Xu N, Jia C, Mao J, et al. Inhibitory effect of verapamil on Candida albicans hyphal development, adhesion and gastrointestinal colonization. FEMS Yeast Res. 2014;14(4):633-41.
  • Yu Q, Xiao C, Zhang K, Jia C, Ding X, Zhang B, et al. The calcium channel blocker verapamil inhibits oxidative stress response in Candida albicans. Mycopathologia. 2014;177(3-4):167-77.
  • Dirim Erdogan D, Aykur M, Selvi Gunel N, Palamar M, Barut Selver O, Ozel B, et al. The Risk Factors and Clinical Features of Acanthamoeba Keratitis: First Time Detection of Acanthamoeba T5 Genotype from Keratitis Patients in Turkey. Acta Parasitologica. 2022;67(3):1384-92.
  • Karakavuk M, Aykur M, Sahar EA, Karakus M, Aldemir D, Donduren O, et al. First time identification of Acanthamoeba genotypes in the cornea samples of wild birds; Is Acanthamoeba keratitis making the predatory birds a target? Experimental parasitology. 2017;183:137-42.
  • Nakaminami H, Tanuma K, Enomoto K, Yoshimura Y, Onuki T, Nihonyanagi S, et al. Evaluation of in vitro antiamoebic activity of antimicrobial agents against clinical Acanthamoeba isolates. Journal of Ocular Pharmacology and Therapeutics. 2017;33(8):629-34.
  • Elder M, Kilvington S, Dart J. A clinicopathologic study of in vitro sensitivity testing and Acanthamoeba keratitis. Investigative ophthalmology & visual science. 1994;35(3):1059-64.
  • Megha K, Sharma M, Sharma C, Gupta A, Sehgal R, Khurana S. Evaluation of in vitro activity of five antimicrobial agents on Acanthamoeba isolates and their toxicity on human corneal epithelium. Eye (Lond). 2022;36(10):1911-7.
  • Mannan Baig A. Identification of chemotherapeutic agents for the treatment of Acanthamoeba infections: rationale for repurposing drugs via the discovery of novel cellular targets: University of Sunderland; 2020.
  • Osato MS, Robinson NM, Wilhelmus KR, Jones DB. In vitro evaluation of antimicrobial compounds for cysticidal activity against Acanthamoeba. Reviews of infectious diseases. 1991;13(Supplement_5):S431-S5.
  • Gupta P, Chanda R, Rai N, Kataria VK, Kumar N. Antihypertensive, amlodipine besilate inhibits growth and biofilm of human fungal pathogen Candida. Assay and Drug Development Technologies. 2016;14(5):291-7.
  • Li Yj, Pan Cz, Zhao Zw, Zhao Zx, Chen Hl, Lu Wb. Effects of a combination of amlodipine and imipenem on 42 clinical isolates of Acinetobacter baumannii obtained from a teaching hospital in Guangzhou, China. BMC infectious diseases. 2013;13:1-9.

Yıl 2023, Cilt: 12 Sayı: 2, 104 - 110, 22.06.2023

Mehmet Aykur

https://doi.org/10.46810/tdfd.1259142

Öz

Kaynakça

  • Khan NA. Acanthamoeba: biology and increasing importance in human health. FEMS microbiology reviews. 2006;30(4):564-95.
  • Marciano-Cabral F, Cabral G. Acanthamoeba spp. as agents of disease in humans. Clinical microbiology reviews. 2003;16(2):273-307.
  • De Jonckheere JF. Ecology of Acanthamoeba. Reviews of infectious diseases. 1991;13 Suppl 5:S385-7.
  • de Lacerda AG, Lira M. Acanthamoeba keratitis: a review of biology, pathophysiology and epidemiology. Ophthalmic Physiol Opt. 2021;41(1):116-35.
  • Putaporntip C, Kuamsab N, Nuprasert W, Rojrung R, Pattanawong U, Tia T, et al. Analysis of Acanthamoeba genotypes from public freshwater sources in Thailand reveals a new genotype, T23 Acanthamoeba bangkokensis sp. nov. Scientific reports. 2021;11(1).
  • Visvesvara GS, Moura H, Schuster FL. Pathogenic and opportunistic free-living amoebae: Acanthamoeba spp., Balamuthia mandrillaris, Naegleria fowleri, and Sappinia diploidea. FEMS immunology and medical microbiology. 2007;50(1):1-26.
  • Radford CF, Bacon AS, Dart JK, Minassian DC. Risk factors for acanthamoeba keratitis in contact lens users: a case-control study. Bmj. 1995;310(6994):1567-70.
  • Carnt N, Hoffman JJ, Verma S, Hau S, Radford CF, Minassian DC, et al. Acanthamoeba keratitis: confirmation of the UK outbreak and a prospective case-control study identifying contributing risk factors. British Journal of Ophthalmology. 2018;102(12):1621-8.
  • Nakaminami H, Tanuma K, Enomoto K, Yoshimura Y, Onuki T, Nihonyanagi S, et al. Evaluation of In Vitro Antiamoebic Activity of Antimicrobial Agents Against Clinical Acanthamoeba Isolates. Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics. 2017.
  • Lorenzo-Morales J, Khan NA, Walochnik J. An update on Acanthamoeba keratitis: diagnosis, pathogenesis and treatment. Parasite. 2015;22:10.
  • Varacalli G, Di Zazzo A, Mori T, Dohlman TH, Spelta S, Coassin M, et al. Challenges in Acanthamoeba Keratitis: A Review. Journal of Clinical Medicine. 2021;10(5).
  • Fanselow N, Sirajuddin N, Yin X-T, Huang AJW, Stuart PM. Acanthamoeba Keratitis, Pathology, Diagnosis and Treatment. Pathogens. 2021;10(3).
  • Carrijo-Carvalho LC, Sant'ana VP, Foronda AS, de Freitas D, de Souza Carvalho FR. Therapeutic agents and biocides for ocular infections by free-living amoebae of Acanthamoeba genus. Surv Ophthalmol. 2017;62(2):203-18.
  • McCoy C, Patel S, Thulasi P. Update on the Management of Acanthamoeba Keratitis. Current Ophthalmology Reports. 2022.
  • Kalra SK, Sharma P, Shyam K, Tejan N, Ghoshal U. Acanthamoeba and its pathogenic role in granulomatous amebic encephalitis. Experimental parasitology. 2020;208.
  • Szentmary N, Daas L, Shi L, Laurik KL, Lepper S, Milioti G, et al. Acanthamoeba keratitis - Clinical signs, differential diagnosis and treatment. J Curr Ophthalmol. 2019;31(1):16-23.
  • Liu S, Yue L, Gu W, Li X, Zhang L, Sun S. Synergistic effect of fluconazole and calcium channel blockers against resistant Candida albicans. PloS one. 2016;11(3):e0150859.
  • Spampinato C, Leonardi D. Candida infections, causes, targets, and resistance mechanisms: traditional and alternative antifungal agents. BioMed research international. 2013;2013.
  • Anwar A, Siddiqui R, Hussain MA, Ahmed D, Shah MR, Khan NA. Silver nanoparticle conjugation affects antiacanthamoebic activities of amphotericin B, nystatin, and fluconazole. Parasitology research. 2018;117(1):265-71.
  • Baig AM, Zohaib R, Nuzair W, Saiqa K, Mehdia N. Evidence of human‐like Ca2+ Channels and Effects of Ca2+ Channel blockers in Acanthamoeba castellanii. Chemical biology & drug design. 2018.
  • Rodrigues AA, Pina-Vaz C, Mardh PA, Martinez-de-Oliveira J, Freitas-da-Fonseca A. Inhibition of germ tube formation by Candida albicans by local anesthetics: an effect related to ionic channel blockade. Current microbiology. 2000;40(3):145-8.
  • Baig AM, Khaleeq A, Nazim F. Targeting CNS Related Protist Pathogens: Calcium Ion Dependency in the Brain-Eating Amoebae. ACS Chem Neurosci. 2019.
  • Baig AM. Drug targeting in Acanthamoeba keratitis: rational of using drugs that are already approved for ocular use in non-keratitis indications. Eye (London, England). 2018.
  • Baig AM, Iqbal J, Khan NA. In vitro efficacy of clinically available drugs against growth and viability of Acanthamoeba castellanii keratitis isolate belonging to the T4 genotype. Antimicrobial agents and chemotherapy. 2013:AAC. 00299-13.
  • Yu Q, Ding X, Zhang B, Xu N, Jia C, Mao J, et al. Inhibitory effect of verapamil on Candida albicans hyphal development, adhesion and gastrointestinal colonization. FEMS Yeast Res. 2014;14(4):633-41.
  • Yu Q, Xiao C, Zhang K, Jia C, Ding X, Zhang B, et al. The calcium channel blocker verapamil inhibits oxidative stress response in Candida albicans. Mycopathologia. 2014;177(3-4):167-77.
  • Dirim Erdogan D, Aykur M, Selvi Gunel N, Palamar M, Barut Selver O, Ozel B, et al. The Risk Factors and Clinical Features of Acanthamoeba Keratitis: First Time Detection of Acanthamoeba T5 Genotype from Keratitis Patients in Turkey. Acta Parasitologica. 2022;67(3):1384-92.
  • Karakavuk M, Aykur M, Sahar EA, Karakus M, Aldemir D, Donduren O, et al. First time identification of Acanthamoeba genotypes in the cornea samples of wild birds; Is Acanthamoeba keratitis making the predatory birds a target? Experimental parasitology. 2017;183:137-42.
  • Nakaminami H, Tanuma K, Enomoto K, Yoshimura Y, Onuki T, Nihonyanagi S, et al. Evaluation of in vitro antiamoebic activity of antimicrobial agents against clinical Acanthamoeba isolates. Journal of Ocular Pharmacology and Therapeutics. 2017;33(8):629-34.
  • Elder M, Kilvington S, Dart J. A clinicopathologic study of in vitro sensitivity testing and Acanthamoeba keratitis. Investigative ophthalmology & visual science. 1994;35(3):1059-64.
  • Megha K, Sharma M, Sharma C, Gupta A, Sehgal R, Khurana S. Evaluation of in vitro activity of five antimicrobial agents on Acanthamoeba isolates and their toxicity on human corneal epithelium. Eye (Lond). 2022;36(10):1911-7.
  • Mannan Baig A. Identification of chemotherapeutic agents for the treatment of Acanthamoeba infections: rationale for repurposing drugs via the discovery of novel cellular targets: University of Sunderland; 2020.
  • Osato MS, Robinson NM, Wilhelmus KR, Jones DB. In vitro evaluation of antimicrobial compounds for cysticidal activity against Acanthamoeba. Reviews of infectious diseases. 1991;13(Supplement_5):S431-S5.
  • Gupta P, Chanda R, Rai N, Kataria VK, Kumar N. Antihypertensive, amlodipine besilate inhibits growth and biofilm of human fungal pathogen Candida. Assay and Drug Development Technologies. 2016;14(5):291-7.
  • Li Yj, Pan Cz, Zhao Zw, Zhao Zx, Chen Hl, Lu Wb. Effects of a combination of amlodipine and imipenem on 42 clinical isolates of Acinetobacter baumannii obtained from a teaching hospital in Guangzhou, China. BMC infectious diseases. 2013;13:1-9.
Toplam 35 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Sağlık Kurumları Yönetimi
Bölüm Makaleler
Yazarlar

Mehmet Aykur 0000-0002-6100-1037

Yayımlanma Tarihi 22 Haziran 2023
Yayımlandığı Sayı Yıl 2023 Cilt: 12 Sayı: 2

Kaynak Göster

APA Aykur, M. (2023). Amoebicidal effect of Fluconazole and Verapamil together against trophozoites and cysts of Acanthamoeba castellanii. Türk Doğa Ve Fen Dergisi, 12(2), 104-110. https://doi.org/10.46810/tdfd.1259142
AMA Aykur M. Amoebicidal effect of Fluconazole and Verapamil together against trophozoites and cysts of Acanthamoeba castellanii. TDFD. Haziran 2023;12(2):104-110. doi:10.46810/tdfd.1259142
Chicago Aykur, Mehmet. “Amoebicidal Effect of Fluconazole and Verapamil Together Against Trophozoites and Cysts of Acanthamoeba Castellanii”. Türk Doğa Ve Fen Dergisi 12, sy. 2 (Haziran 2023): 104-10. https://doi.org/10.46810/tdfd.1259142.
EndNote Aykur M (01 Haziran 2023) Amoebicidal effect of Fluconazole and Verapamil together against trophozoites and cysts of Acanthamoeba castellanii. Türk Doğa ve Fen Dergisi 12 2 104–110.
IEEE M. Aykur, “Amoebicidal effect of Fluconazole and Verapamil together against trophozoites and cysts of Acanthamoeba castellanii”, TDFD, c. 12, sy. 2, ss. 104–110, 2023, doi: 10.46810/tdfd.1259142.
ISNAD Aykur, Mehmet. “Amoebicidal Effect of Fluconazole and Verapamil Together Against Trophozoites and Cysts of Acanthamoeba Castellanii”. Türk Doğa ve Fen Dergisi 12/2 (Haziran 2023), 104-110. https://doi.org/10.46810/tdfd.1259142.
JAMA Aykur M. Amoebicidal effect of Fluconazole and Verapamil together against trophozoites and cysts of Acanthamoeba castellanii. TDFD. 2023;12:104–110.
MLA Aykur, Mehmet. “Amoebicidal Effect of Fluconazole and Verapamil Together Against Trophozoites and Cysts of Acanthamoeba Castellanii”. Türk Doğa Ve Fen Dergisi, c. 12, sy. 2, 2023, ss. 104-10, doi:10.46810/tdfd.1259142.
Vancouver Aykur M. Amoebicidal effect of Fluconazole and Verapamil together against trophozoites and cysts of Acanthamoeba castellanii. TDFD. 2023;12(2):104-10.
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