Bioinformatics analysis of the presence of Ca2+ channels of Acanthamoeba castellanii
Bioinformatics analysis
DOI:
https://doi.org/10.5281/zenodo.11455721Keywords:
Bioinformatics tools, Acanthamoeba castellanii, Ca2+ channels, new therapeutic targetsAbstract
The free-living amoeba (FLA) belonging to the genus Acanthamoeba is the most widespread protozoan in the environment, found in natural and man-made environments. Acanthamoeba is an opportunistic protist capable of causing granulomatous amebic encephalitis (GAE), a fatal disease of the central nervous system (CNS), and Acanthamoeba keratitis (AK), a painful, progressive, and sight-threatening infection. A single drug that can simultaneously eliminate both trophozoite and cystic forms of the parasite is currently unavailable. Bioinformatics research has aimed to reveal the presence of new therapeutic targets and pathways in the treatment of Acanthamoeba.
Calcium (Ca2+) channels regulate many vital functions within cells. Ca2+ influx mediates the regulation of physiological signaling pathways in parasites. Calcium channels in Acanthamoeba allow the intracellular Ca2+ stores to be refilled following intracellular Ca2+ release. It is also well known that the role of calcium in the activation of some anti-parasitic drugs is very important. The search for protein sequence homology between two-pore calcium channel protein 1 (TPC-1), TPC-2, and calmodulin was done by searching the Acanthamoeba Neff strain protein databases at NCBI and amoebadb.org by using BLASTp search. The BLASTp alignment option was selected to show similarities between the proteins of both species.
In conclusion, it may be an option for a narrow treatment approach for GAE and AK caused by Acanthamoeba species; therefore, the discovery of calcium channels (TPC-1, TPC-2, and Calmodulin) in Acanthamoeba could prove to be a potential therapeutic target in the future.
Downloads
References
Khan NA. Acanthamoeba: biology and increasing importance in human health. FEMS Microbiol Rev. 2006;30(4):564-595. https://doi.org/10.1111/j.1574-6976.2006.00023.x
Lorenzo-Morales JCM, Martin-Navarro A, Lopez-Arencibia F, Arnalich-Montiel JE, Pinero and B. Valladares. Acanthamoeba keratitis: an emerging disease gathering importance worldwide? Trends Parasitol. 2013;29(4):181-187. https://doi.org/10.1016/j.pt.2013.01.006
Duggal SS, Rongpharpi A, Duggal A, Kumar and I Biswal. Role of Acanthamoeba in granulomatous encephalitis: a review. J Infect Dis Immune Ther. 2017;1:1-2. https://doi.org/10.3389/fmicb.2023.1147077
Ahmed UA, Anwar SK, Ong A, Anwar and NA Khan. Applications of medicinal chemistry for drug discovery against Acanthamoeba infections. Med Res Rev. 2022:42(1):462-512. https://doi.org/10.1002/med.21851
Clarke BA, Sinha DN, Parmar and E Sykakis. Advances in the diagnosis and treatment of acanthamoeba keratitis. J Ophthalmol. 2012:484892. https://doi.org/10.1155/2012/484892
Szentmary NL, Daas, L Shi, KL Laurik, S Lepper, G Milioti and B Seitz. Acanthamoeba keratitis - Clinical signs, differential diagnosis and treatment. J Curr Ophthalmol. 2019:31(1):16-23. https://doi.org/10.1016/j.joco.2018.09.008
Yamakage M and A Namiki. Calcium channels—basic aspects of their structure, function and gene encoding; anesthetic action on the channels—a review. Canadian Journal of Anesthesia. 2002:49(2):151-164. https://doi.org/10.1007/BF03020488
Scarpelli PH, MF Pecenin and CR Garcia. Intracellular Ca2+ signaling in protozoan parasites: an overview with a focus on mitochondria. International Journal of Molecular Sciences. 2021:22(1):469. https://doi.org/10.3390/ijms22010469
King MM, BB Kayastha, MJ Franklin and MA Patrauchan. Calcium regulation of bacterial virulence. Calcium Signaling. 2020:827-855. https://doi.org/10.1007/978-3-030-12457-1_33
Baig AM, A Khaleeq and F Nazim. Targeting CNS Related Protist Pathogens: Calcium Ion Dependency in the Brain-Eating Amoebae. ACS Chem Neurosci. 2019. https://doi.org/10.1021/acschemneuro.9b00635
Altschul SF, W Gish, W Miller, EW Myers and DJ Lipman. Basic local alignment search tool. Journal of molecular biology. 1990:215(3):403-410. https://doi.org/10.1016/S0022-2836(05)80360-2
Consortium U. UniProt: a hub for protein information. Nucleic acids research. 2015:43(D1):D204-D212. https://doi.org/10.1093/nar/gku989
Aurrecoechea C, A Barreto, EY Basenko, J Brestelli, BP Brunk, S Cade, K Crouch, R Doherty, D Falke and S Fischer. EuPathDB: the eukaryotic pathogen genomics database resource. Nucleic acids research. 2017:45(D1):D581-D591. https://doi.org/10.1093/nar/gkw1105
Stoesser G, W Baker, A van den Broek, E Camon, M Garcia-Pastor, C Kanz, T Kulikova, R Leinonen, Q Lin and V Lombard. The EMBL nucleotide sequence database. Nucleic acids research. 2002:30(1):21-26. https://doi.org/10.1093/nar/30.1.21
Biasini M, S Bienert, A Waterhouse, K Arnold, G Studer, T Schmidt, F Kiefer, TG Cassarino, M Bertoni and L Bordoli. SWISS-MODEL: modelling protein tertiary and quaternary structure using evolutionary information. Nucleic acids research. 2014:42(W1):W252-W258. https://doi.org/10.1093/nar/gku340
Kelley LA, S Mezulis, CM Yates, MN Wass and MJ Sternberg. The Phyre2 web portal for protein modeling, prediction and analysis. Nature protocols. 2015:10(6):845-858. https://doi.org/10.1038/nprot.2015.053
M Baig, AZ Rana, M Mannan, S Tariq and HR Ahmad. Antibiotic Effects of Loperamide: Homology of Human Targets of Loperamide with Targets in Acanthamoeba spp. Recent Patents on Anti-Infective Drug Discovery. 2017a:12(1):44-60. https://doi.org/10.2174/1574891X12666170425170544
M Baig, AZ Rana, SS Tariq and FR Ahmad. Bioinformatic insights on target receptors of amiodarone in human and Acanthamoeba castellanii. Infectious Disorders-Drug Targets (Formerly Current Drug Targets-Infectious Disorders). 2017b:17(3):160-177. https://doi.org/10.2174/1871526517666170622075154.
Brunton LL, R Hilal-Dandan and BC Knollmann. The pharmacological basis of therapeutics. Goodman. 2018:11:1280-1281.
de Souza W, Rodrigues JC. Sterol Biosynthesis Pathway as Target for Anti-trypanosomatid Drugs. Interdiscip Perspect Infect Dis. 2009:642502. https://doi.org/10.1155/2009/642502
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.