Abstract
The genus Acanthamoeba can cause Acanthamoeba keratitis (AK) and granulomatous amoebic encephalitis (GAE). The treatment of these illnesses is hampered by the existence of a resistance stage that many times causes infection relapses. In an attempt to add new agents to our chemotherapeutic arsenal against acanthamebiasis, two Acanthamoeba isolates were treated in vitro with newly synthesized biguanide dendrimers. Trophozoite viability analysis and ultrastructural studies showed that dendrimers prevent encystment by lysing the cellular membrane of the amoeba. Moreover, one of the dendrimers showed low toxicity when tested on mammalian cell cultures, which suggest that it might be eventually used as an amoebicidal drug or as a disinfection compound in contact lens solutions.
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References
Arnalich-Montiel F, Lumbreras-Fernández B, Martín-Navarro CM, Valladares B, Lopez-Velez R, Morcillo-Laiz R, Lorenzo-Morales J (2014) Influence of Acanthamoeba genotype on clinical course and outcomes of patients with Acanthamoeba keratitis in Spain. J Clin Microbiol 52:1213–1216. https://doi.org/10.1128/JCM.00031-14
Baig AM, Iqbal J, Khan NA (2013) In vitro efficacy of clinically available drugs against growth and viability of Acanthamoeba castellanii keratitis isolate belonging to the T4 genotype. Antimicrob Agents Chemother 57(8):3561–3567. https://doi.org/10.1128/AAC.00299-13
Bang S, Edell E, Eghrari AO, Gottsch JD (2010) Treatment with voriconazole in 3 eyes with resistant Acanthamoeba keratitis. Am J Ophthalmol 149(1):66–69. https://doi.org/10.1016/j.ajo.2009.08.004
Bermejo JF, Ortega P, Chonco L, Eritja R, Samaniego R, Müllner M, de Jesus E, de la Mata FJ, Flores JC, Gómez R, Muñoz-Fernández MA (2007) Water-soluble carbosilane dendrimers: synthesis biocompatibility and complexation with oligonucleotides; evaluation for medical applications. Chem Eur J 13(2):483–495. https://doi.org/10.1002/chem.200600594
Cabello-Vílchez AM, Martín-Navarro CM, López-Arencibia A, Reyes-Batlle M, Sifaoui I, Valladares B, Piñero JE, Lorenzo-Morales J (2014) Voriconazole as a first-line treatment against potentially pathogenic Acanthamoeba strains from Peru. Parasitol Res 113(2):755–759. https://doi.org/10.1007/s00436-013-3705-8
Chen CZ, Cooper SL (2000) Recent advances in antimicrobial dendrimers. Adv Mater 12(11):843–846. https://doi.org/10.1002/(SICI)1521-4095(200006)12:11<843::AID-ADMA843>3.0.CO;2-T
Costa de Aguiar AP, Oliveira-Silveira C, Todero-Winck MA, Brittes-Rott M (2013) Susceptibility of Acanthamoeba to multipurpose lens-cleaning solutions. Acta Parasitol 58:304–308
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(8):2689–2697. https://doi.org/10.1128/JCM.00309-10
Fuentes-Paniagua E, Hernández-Ros JM, Soliveri J, Copa-Patiño JL, Gómez R, Sánchez-Nieves J, de la Mata FJ (2017) Strategies for penicillin V dendronization with cationic carbosilane dendrons and study of antibacterial properties. Can J Chem 95(9):927–934. https://doi.org/10.1139/cjc-2017-0059
Heredero-Bermejo I, Copa-Patiño JL, Soliveri J, García-Gallego S, Rasines B, Gómez R, Pérez-Serrano J (2013) In vitro evaluation of the effectiveness of new water-stable cationic carbosilane dendrimers against Acanthamoeba castellanii UAH-T17c3 trophozoites. Parasitol Res 112(3):961–969. https://doi.org/10.1007/s00436-012-3216-z
Heredero-Bermejo I, Criado-Fornelio A, De Fuentes I, Soliveri J, Copa-Patiño JL, Pérez-Serrano J (2015a) Characterization of a human–pathogenic Acanthamoeba griffini isolated from a contact lens-wearing keratitis patient in Spain. Parasitology 142(2):363–373
Heredero-Bermejo I, Copa-Patiño JL, Soliveri J, Fuentes-Paniagua E, de la Mata FJ, Gomez R, Perez-Serrano J (2015b) Evaluation of the activity of new cationic carbosilane dendrimers on trophozoites and cysts of Acanthamoeba polyphaga. Parasitol Res 114(2):473–486
Heredero-Bermejo I, Sanchez-Nieves J, Soliveri J, Gomez R, de la Mata FJ, Copa-Patino JL, Perez-Serrano J (2016) In vitro anti-Acanthamoeba synergistic effect of chlorhexidine and cationic carbosilane dendrimers against both trophozoite and cyst forms. Int J Pharm 509(1–2):1–7
Heredero-Bermejo I, Hernández-Ros JM, Sánchez-García L, Maly M, Verdú-Expósito C, Soliveri J, de la Mata FJ, Copa-Patiño JL, Pérez-Serrano J, Sánchez-Nieves J, Gómez R (2018) Ammonium and guanidine carbosilane dendrimers and dendrons as microbicides. Eur Polym J 101:159–168. https://doi.org/10.1016/j.eurpolymj.2018.02.025
Ibrahim YW, Boase DL, Cree IA (2009) How could contact Lens wearers be at risk of Acanthamoeba infection? A review. J Optom 2:60–66. https://doi.org/10.3921/joptom.2009.60
Iovieno A, Oechsler RA, Ledee DR, Miller D, Alfonso EC (2010) Drug-resistant severe Acanthamoeba keratitis caused by rare T5 Acanthamoeba genotype. Eye Contact Lens 36(3):183–184. https://doi.org/10.1097/ICL.0b013e3181da2350
Johnston SP, Sriram R, Qvarnstrom Y, Roy S, Verani J, Yoder J, Lorick S, Roberts J, Beach MJ, Visvesvara G (2009) Resistance of Acanthamoeba cysts to disinfection in multiple contact lens solutions. J Clin Microbiol 47:2040–2045. https://doi.org/10.1128/JCM.00575-09
Krupková A, Čermák J (2010) Structural defects in polyallylcarbosilane dendrimers and their polyol derivatives characterized by NMR and MALDI-TOF mass spectrometry. Macromolecules 43:4511–4519. https://doi.org/10.1021/ma100315w
Kuźma Ł, Derda M, Hadaś E, Wysokińska H (2015) Abietane diterpenoids from Salvia sclarea transformed roots as growth inhibitors of pathogenic Acanthamoeba spp. Parasitol Res 114(1):323–327. https://doi.org/10.1007/s00436-014-4211-3
Marciano-Cabral F, Cabral G (2003) Acanthamoeba sp. as agents of disease in humans. Clin Microbiol Rev 16:273–307. https://doi.org/10.1128/CMR.16.2.273-307.2003
Maroto-Díaz M, Elie BT, Gómez-Sal P, Pérez-Serrano J, Gómez R, Contel M, de la Mata FJ (2016) Synthesis and anticancer activity of carbosilane metallodendrimers based on arene ruthenium (ii) complexes. Dalton Trans 45(16):7049–7066. https://doi.org/10.1039/C6DT00465B
Martín-Navarro CM, López-Arencibia A, Arnalich-Montiel F, Valladares B, Piñero JE, Lorenzo-Morales J (2013) Evaluation of the in vitro activity of commercially available moxifloxacin and voriconazole eye-drops against clinical strains of Acanthamoeba. Graefes Arch Clin Exp Opthalmol 251(9):2111–2117
Maycock NJ, Jayaswal R (2016) Update on Acanthamoeba keratitis: diagnosis, treatment, and outcomes. Cornea 35(5):713–720. https://doi.org/10.1097/ICO.0000000000000804
Mayer S, Daigle DM, Brown ED, Khatri J, Organ MG (2004) An expedient and facile one-step synthesis of a biguanide library by microwave irradiation coupled with simple product filtration. Inhibitors of dihydrofolate reductase. J Comb Chem 6(5):776–782. https://doi.org/10.1021/cc049953+
Mlynarczyk DT, Kocki T, Goslinski T (2017) Dendrimer structure diversity and tailorability as a way to fight infectious diseases. In Nanostructured Materials-Fabrication to Applications. (ed) InTech, pp 111–134
Moon EK, Park HR, Quan FS, Kong HH (2016) Efficacy of Korean multipurpose contact lens disinfecting solutions against Acanthamoeba castellanii. Korean J Parasitol 54:697–702. https://doi.org/10.3347/kjp.2016.54.6.697
Moreno S, Lozano-Cruz T, Ortega P, Tarazona MP, de la Mata FJ, Gómez R (2014) Synthesis of new amphiphilic water-stable hyperbranched polycarbosilane polymers. Polym Int 63(7):1311–1323. https://doi.org/10.1002/pi.4679
Ortega P, Copa-Patiño JL, Muñoz-Fernández MA, Soliveri J, Gómez R, de la Mata FJ (2008) Amine and ammonium functionalization of chloromethylsilane-ended dendrimers. Antimicrobial activity studies. Org Biomol Chem 6:3264–3269. https://doi.org/10.1039/b809569h
Ortega P, Cobaleda BM, Hernández-Ros JM, Fuentes-Paniagua E, Sánchez-Nieves J, Tarazona MP, Copa-Patiño JL, Soliveri J, de la Mata FJ, Gómez R (2011) Hyperbranched polymers versus dendrimers containing a carbosilane framework and terminal ammonium groups as antimicrobial agents. Org Biomol Chem 9(14):5238–5248. https://doi.org/10.1039/c1ob05321c
Pacella E, La Torre G, De Giusti M, Brillante C, Lombardi AM, Smaldone G, Pacella F (2013) Results of case-control studies support the association between contact lens use and Acanthamoeba keratitis. Clin Ophthalmol 7:991. https://doi.org/10.2147/OPTH.S43471
Rasines B, Hernández-Ros JM, de las Cuevas N, Copa-Patiño JL, Soliveri J, Muñoz-Fernández MA, Gómez R, de la Mata FJ (2009) Water-stable ammonium-terminated carbosilane dendrimers as efficient antibacterial agents. Dalton Trans:8704–8713. https://doi.org/10.1039/b909955g
Shoff ME, Joslin CE, Tu EY, Kubatko L, Fuerst PA (2008) Efficacy of contact lens systems against recent clinical and tap water Acanthamoeba isolates. Cornea 27:713–719. https://doi.org/10.1097/QAI.0b013e31815e7251
Walochnik J, Obwaller A, Gruber F, Mildner M, Tschachler E, Suchomel M, Auer H (2009) Anti-Acanthamoeba efficacy and toxicity of miltefosine in an organotypic skin equivalent. J Antimicrob Chemother 64(3):539–545. https://doi.org/10.1093/jac/dkp215
Acknowledgments
We wish to thank Antonio Priego and Mr. José Antonio Pérez (Microscopy Unit–CAI Medicina y Biología de la Universidad de Alcalá) for assistance with scanning electron microscopy and Ángel Pueblas (Photography Unit–CAI Medicina y Biología de la Universidad de Alcalá) for expert help with photographic work.
Funding
This work was supported by grants CTQ2017-86224-P (from MINECO), Consortium NANODENDMED-II-CM (B2017/BMD-3703), IMMUNOTHERCAN-CM (B2017/BMD3733), and Universidad de Alcalá CCG2016/BIO-023. CIBER-BBN as an initiative funded by the VI National R&D&i Plan 2008–2011, Iniciativa Ingenio 2010, Consolider Program, CIBER Actions, and financed by the Instituto de Salud Carlos III with assistance from the European Regional Development Fund.
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Martín-Pérez, T., Lozano-Cruz, T., Criado-Fornelio, A. et al. Synthesis and in vitro activity of new biguanide-containing dendrimers on pathogenic isolates of Acanthamoeba polyphaga and Acanthamoeba griffini. Parasitol Res 118, 1953–1961 (2019). https://doi.org/10.1007/s00436-019-06341-7
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DOI: https://doi.org/10.1007/s00436-019-06341-7