The emerging paradigm of calcium homeostasis as a new therapeutic target for protozoan parasites.
Leishmania
Plasmodium
SERCA and non-SERCA pump inhibitors
Toxoplasma
Trypanosoma
apicomplexa
calcium channel modulators
calcium homeostasis
cryptosporidium
drug resistance
kinetoplastida
protozoan parasites
target-based drug discovery
Journal
Medicinal research reviews
ISSN: 1098-1128
Titre abrégé: Med Res Rev
Pays: United States
ID NLM: 8103150
Informations de publication
Date de publication:
01 2022
01 2022
Historique:
revised:
10
10
2020
received:
11
05
2020
accepted:
31
03
2021
pubmed:
15
4
2021
medline:
5
4
2022
entrez:
14
4
2021
Statut:
ppublish
Résumé
Calcium channels (CCs), a group of ubiquitously expressed membrane proteins, are involved in many pathophysiological processes of protozoan parasites. Our understanding of CCs in cell signaling, organelle function, cellular homeostasis, and cell cycle control has led to improved insights into their structure and functions. In this article, we discuss CCs characteristics of five major protozoan parasites Plasmodium, Leishmania, Toxoplasma, Trypanosoma, and Cryptosporidium. We provide a comprehensive review of current antiparasitic drugs and the potential of using CCs as new therapeutic targets. Interestingly, previous studies have demonstrated that human CC modulators can kill or sensitize parasites to antiparasitic drugs. Still, none of the parasite CCs, pumps, or transporters has been validated as drug targets. Information for this review draws from extensive data mining of genome sequences, chemical library screenings, and drug design studies. Parasitic resistance to currently approved therapeutics is a serious and emerging threat to both disease control and management efforts. In this article, we suggest that the disruption of calcium homeostasis may be an effective approach to develop new anti-parasite drug candidates and reduce parasite resistance.
Substances chimiques
Calcium
SY7Q814VUP
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
56-82Informations de copyright
© 2021 Wiley Periodicals LLC.
Références
Organization WH, others World Malaria Report 2019. Geneva: World Health organization; 2019:. https://www.who.int/publications/i/item/9789241565721
Mace KE. Malaria surveillance-United States. MMWR Surveill Summ. 2016:68.
Chen I, Cooney R, Feachem RG, Lal A, Mpanju-Shumbusho W. The Lancet Commission on malaria eradication. The Lancet. 2018;391(10130):1556-1558.
Andrews KT, Fisher G, Skinner-Adams TS. Drug repurposing and human parasitic protozoan diseases. Int J Parasitol Drugs Drug Resist. 2014;4(2):95-111.
Achieng AO, Rawat M, Ogutu B, et al. Molecular drug targets and mechanism of action. Curr Top Med Chem. 2017;17(19):2114-2128.
Gupta Y, Gupta N, Singh S, et al. Multistage inhibitors of the malaria parasite: emerging hope for chemoprotection and malaria eradication. Med Res Rev. 2018;38(5):1511-1535.
Kumar Singh A, Rajendran V, Singh S, et al. Antiplasmodial activity of hydroxyethylamine analogs: synthesis, biological activity and structure activity relationship of plasmepsin inhibitors. Bioorg Med Chem. 2018;26(13):3837-3844.
Sharma N, Verma A, Poonam F, Kempaiah P, Rathi B. Chemical libraries targeting liver stage malarial infection. Chem Biol Lett. 2019;6(1):14-22.
Singh S, Rajendran V, He J, et al. Fast-acting small molecules targeting malarial aspartyl proteases, plasmepsins, inhibit malaria infection at multiple life stages. ACS Infect Dis. 2019;5(2):184-198.
Hay SI, Abajobir AA, Abate KH, et al. Global, regional, and national disability-adjusted life-years (DALYs) for 333 diseases and injuries and healthy life expectancy (HALE) for 195 countries and territories, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. The Lancet. 2017;390(10100):1260-1344.
World Health Organization W. WHO Factsheet; Leishmaniasis (2019).
Prevention C-C for DC and. CDC - ChagWorld Health Organization W. WHO Factsheet; Leishmaniasisas Disease - Epidemiology & Risk Factors. https://www.cdc.gov/parasites/chagas/epi.html (2019. Accessed February 12, 2020).
CDC - African Trypanosomiasis - Epidemiology & Risk Factors. https://www.cdc.gov/parasites/sleepingsickness/epi.html (2019. Accessed February 12, 2020).
Prevention C-C for DC and. CDC - Toxoplasmosis - Epidemiology & Risk Factors. https://www.cdc.gov/parasites/toxoplasmosis/epi.html (2019. Accessed February 12, 2020).
Prevention C-C for DC and CDC - Cryptosporidiosis - Diagnosis. https://www.cdc.gov/parasites/crypto/infection-sources.html (2019. Accessed February 12, 2020).
CDC - Parasites - Malaria. https://www.cdc.gov/parasites/malaria/index.html (2019. Accessed February 12, 2020).
WHO WHO, others. World Malaria Report; 2019 [Epub ahead of print].
Das S, Saha B, Hati AK, Roy S. Evidence of artemisinin-resistant Plasmodium falciparum malaria in eastern India. N Engl J Med. 2018;379(20):1962-1964.
World Health Organization. 2018. Others. Leishmaniasis. 2019.
Satoskar A, Durvasula R. Pathogenesis of Leishmaniasis. Springer; 2016. http://doi.org/10.1007/978-1-4614-9108-8
Bailey F, Mondragon-Shem K, Haines LR, et al Cutaneous leishmaniasis and co-morbid major depressive disorder: a systematic review with burden estimates. PLoS Negl Trop Dis. 2019;13(2):e0007092.
Prevention C-C for DC and. CDC - Leishmaniasis - Epidemiology & Risk Factors. https://www.cdc.gov/parasites/leishmaniasis/epi.html (2019. Accessed February 12, 2020).
Chakravarty J, Sundar S. Drug resistance in leishmaniasis. J Glob Infect Dis. 2010;2(2):167.
Ponte-Sucre A, Gamarro F, Dujardin J-C, et al. Drug resistance and treatment failure in leishmaniasis: a 21st century challenge. PLoS Negl Trop Dis. 2017;11(12):e0006052.
Prevention C-C for DC and. CDC - Chagas Disease - Detailed Fact Sheet. https://www.cdc.gov/parasites/chagas/gen_info/detailed.html (2019. Accessed February 12, 2020).
Nunes FMM. Prevalência de síndrome metabólica em pacientes com doença de Chagas nas formas cardíaca e indeterminada [Epub ahead of print].
Ryan U, Fayer R, Xiao L. Cryptosporidium species in humans and animals: current understanding and research needs. Parasitology. 2014;141(13):1667-1685.
Efstratiou A, Ongerth JE, Karanis P. Waterborne transmission of protozoan parasites: review of worldwide outbreaks-an update 2011-2016. Water Res. 2017;114:11414-11422.
Manjunatha UH, Chao AT, Leong FJ, Diagana TT. Cryptosporidiosis drug discovery: opportunities and challenges. ACS Infect Dis. 2016;2(8):530-537.
Kramer MH, Herwaldt BL, Craun GF, Calderon RL, Juranek DD. Surveillance for waterborne-disease outbreaks-United States, 1993-1994 [Epub ahead of print]. 1996. https://stacks.cdc.gov/view/cdc/26708
Bhalchandra S, Cardenas D, Ward HD. Recent breakthroughs and ongoing limitations in Cryptosporidium research. F1000Research. 2018:7.
Casemore D, Sands R, Curry A. Cryptosporidium species a" new" human pathogen. J Clin Pathol. 1985;38(12):1321-1336.
Shrivastava AK, Panda S, Kumar S, Sahu PS. Two novel genomic DNA sequences as common diagnostic targets to detect Cryptosporidium hominis and Cryptosporidium parvum: Development of quantitative polymerase chain reaction assays, and clinical evaluation. Indian J Med Microbiol. 2020;38(3&4):430-439.
Shrivastava AK, Kumar S, Smith WA, Sahu PS. Revisiting the global problem of cryptosporidiosis and recommendations. Trop Parasitol. 2017;7(1):8.
Reithinger R, Dujardin J-C, Louzir H, Pirmez C, Alexander B, Brooker S. Cutaneous leishmaniasis. Lancet Infect Dis. 2007;7(9):581-596.
Barrett MP, Croft SL. Management of trypanosomiasis and leishmaniasis. Br Med Bull. 2012;104(1):175-196.
Odiit M, Kansiime F, Enyaru J. Duration of symptoms and case fatality of sleeping sickness caused by Trypanosoma brucei rhodesiense in Tororo, Uganda. East Afr Med J. 1997;74(12):792-795.
Kennedy PG. Clinical features, diagnosis, and treatment of human African trypanosomiasis (sleeping sickness). Lancet Neurol. 2013;12(2):186-194.
Cook TB, Brenner LA, Cloninger CR, et al. “Latent” infection with Toxoplasma gondii: association with trait aggression and impulsivity in healthy adults. J Psychiatr Res. 2015;60:6087-6094.
Fekadu A, Shibre T, Cleare AJ. Toxoplasmosis as a cause for behaviour disorders-overview of evidence and mechanisms. Folia Parasitol. 2010;57(2):105-113.
Gajewski PD, Falkenstein M, Hengstler JG, Golka K. Toxoplasma gondii impairs memory in infected seniors. Brain Behav Immun. 2014;36:36193-36199.
Pearce BD, Hubbard S, Rivera HN, et al. Toxoplasma gondii exposure affects neural processing speed as measured by acoustic startle latency in schizophrenia and controls. Schizophr Res. 2013;150(1):258-261.
Chen X-M, Keithly JS, Paya CV, LaRusso NF. Cryptosporidiosis. N Engl J Med. 2002;346(22):1723-1731.
Hedstrom L. Cryptosporidium: a first step toward tractability. Trends Parasitol. 2015;31(9):401-402.
Bohne W, Heesemann J, Gross U. Reduced replication of Toxoplasma gondii is necessary for induction of bradyzoite-specific antigens: a possible role for nitric oxide in triggering stage conversion. Infect Immun. 1994;62(5):1761-1767.
Jin Z, Ma J, Zhu G, Zhang H. Discovery of novel anti-cryptosporidial activities from natural products by in vitro high-throughput phenotypic screening. Front Microbiol. 2019;10:101999.
Rossignol J-F. Cryptosporidium and Giardia: treatment options and prospects for new drugs. Exp Parasitol. 2010;124(1):45-53.
Eckstein-Ludwig U, Webb R, Van Goethem I, et al. Artemisinins target the SERCA of Plasmodium falciparum. Nature. 2003;424(6951):957-961.
Maragos CM. Complexation of the mycotoxin cyclopiazonic acid with lanthanides yields luminescent products. Toxins. 2018;10(7):285.
Pinto-Martinez AK, Rodriguez-Durán J, Serrano-Martin X, Hernandez-Rodriguez V, Benaim G. Mechanism of action of miltefosine on Leishmania donovani involves the impairment of acidocalcisome function and the activation of the sphingosine-dependent plasma membrane Ca2+ channel. Antimicrob Agents Chemother. 2018;62(1):e01614-e01617.
Benaim G, Lopez-Estrano C, Docampo R, Moreno S. A calmodulin-stimulated Ca2+ pump in plasma-membrane vesicles from Trypanosoma brucei; selective inhibition by pentamidine. Biochem J. 1993;296(3):759-763.
Gotsbacher MP, Cho SM, Kim NH, Liu F, Kwon HJ, Karuso P. Reverse chemical proteomics identifies an unanticipated human target of the antimalarial artesunate. ACS Chem Biol. 2019;14(4):636-643.
Leong FJ, Li R, Jain JP, et al. A first-in-human randomized, double-blind, placebo-controlled, single-and multiple-ascending oral dose study of novel antimalarial Spiroindolone KAE609 (Cipargamin) to assess its safety, tolerability, and pharmacokinetics in healthy adult volunteers. Antimicrob Agents Chemother. 2014;58(10):6209-6214.
Elmahallawy EK, Jiménez-Aranda A, Martínez AS, et al. Activity of melatonin against Leishmania infantum promastigotes by mitochondrial dependent pathway. Chem Biol Interact. 2014;220:22084-22093.
Oryan A, Bemani E, Bahrami S. Emerging role of amiodarone and dronedarone, as antiarrhythmic drugs, in treatment of leishmaniasis. Acta Trop. 2018;185:18534-18541.
Laura Sbaraglini M, Cristina Vanrell M, Leticia Bellera C, et al. Neglected tropical protozoan diseases: drug repositioning as a rational option. Curr Top Med Chem. 2016;16(19):2201-2222.
Reimão JQ, Mesquita JT, Ferreira DD, Tempone AG. Investigation of calcium channel blockers as antiprotozoal agents and their interference in the metabolism of Leishmania (L.) infantum. Evid Based Complement Alternat Med. 2016;2016:1-9.
van der Hoeven D, Cho K, Ma X, Chigurupati S, Parton RG, Hancock JF. Fendiline inhibits K-Ras plasma membrane localization and blocks K-Ras signal transmission. Mol Cell Biol. 2013;33(2):237-251.
Menezes C, Kirchgatter K, Di Santi SM, et al. In vitro evaluation of verapamil and other modulating agents in Brazilian chloroquine-resistant Plasmodium falciparum isolates. Rev Soc Bras Med Trop. 2003;36(1):5-9.
Núñez-Vergara Luis J., Squella J.A., Bollo-Dragnic Soledad, Marín-Catalán R., Pino L., Diaz-Araya G., Letelier M.E.. Isradipine and lacidipine: Effects in vivo and in vitro on Trypanosoma cruzi epimastigotes. General Pharmacology: The Vascular System. 1998;30 (1):85-87. http://dx.doi.org/10.1016/s0306-3623(97)00077-3
Rout S, Mahapatra RK. Plasmodium falciparum: multidrug resistance. Chem Biol Drug Des. 2019;93(5):737-759.
Wilson CM, Volkman SK, Thaithong S, et al. Amplification of pfmdr1 associated with mefloquine and halofantrine resistance in Plasmodium falciparum from Thailand. Mol Biochem Parasitol. 1993;57(1):151-160.
Rønn A, Msangeni H, Mhina J, Wernsdorfer W, Bygbjerg I. High level of resistance of Plasmodium falciparum to sulfadoxine-pyrimethamine in children in Tanzania. Trans R Soc Trop Med Hyg. 1996;90(2):179-181.
Tan KR, Magill AJ, Parise ME, Arguin PM. Doxycycline for malaria chemoprophylaxis and treatment: report from the CDC expert meeting on malaria chemoprophylaxis. Am J Trop Med Hyg. 2011;84(4):517-531.
Mejía-Jaramillo AM, Fernández GJ, Montilla M, Nicholls RS, Triana-Chávez O. Sensibilidad al benzonidazol de cepas de Trypanosoma cruzi sugiere la circulación de cepas naturalmente resistentes en Colombia. Biomédica. 2012;32(2):196-205.
Montazeri M, Mehrzadi S, Sharif M, et al. Drug resistance in Toxoplasma gondii. Front Microbiol. 2018;9:92587.
Henry M, Alibert S, Orlandi-Pradines E, et al. Chloroquine resistance reversal agents as promising antimalarial drugs. Curr Drug Targets. 2006;7(8):935-948.
Herwaldt BL, Dougherty CP, Allen CK, et al. Characteristics of patients for whom benznidazole was released through the CDC-sponsored investigational New Drug Program for Treatment of Chagas Disease-United States, 2011-2018. Morb Mortal Wkly Rep. 2018;67(29):803-805.
Torresi J, McGuinness S, Leder K, et al. Malaria prevention. Manual of Travel Medicine. 4th ed. Singapore: Springer; 2019:171-205.
Panel on Antiretrolviral Guidelines for Adults and Adolescents. 2019. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Available https://clinicalinfo.hiv.gov/sites/default/files/guidelines/documents/AdultandAdolescentGL.pdf
Khare P, Jaiswal AK, Tripathi CDP, Joshi S, Sundar S, Dube A. Efficacy of Leishmania donovani trypanothione reductase, identified as a potent Th1 stimulatory protein, for its immunogenicity and prophylactic potential against experimental visceral leishmaniasis. Parasitol Res. 2014;113(3):851-862.
World Health Organization. 2019. Others. WHO malaria policy advisory committee (MPAC) meeting: meeting report.
Haldar K, Bhattacharjee S, Safeukui I. Drug resistance in Plasmodium. Nat Rev Microbiol. 2018;16(3):156-170.
Tiwari MK, Chaudhary S. Artemisinin-derived antimalarial endoperoxides from bench-side to bed-side: chronological advancements and future challenges. Med Res Rev. 2020;40(4):1220-1275.
Hefnawy A, Berg M, Dujardin J-C, De Muylder G. Exploiting knowledge on Leishmania drug resistance to support the quest for new drugs. Trends Parasitol. 2017;33(3):162-174.
Lutgring JD, Machado M-J, Benahmed FH, et al. FDA-CDC antimicrobial resistance isolate bank: a publicly available resource to support research, development, and regulatory requirements. J Clin Microbiol. 2018;56(2):e01415-e01417.
Espada CR, Magalhães RM, Cruz MC, et al. Investigation of the pathways related to intrinsic miltefosine tolerance in Leishmania (Viannia) braziliensis clinical isolates reveals differences in drug uptake. Int J Parasitol Drugs Drug Resist. 2019;11:11139-11147.
García-Hernández R, Manzano JI, Castanys S, Gamarro F. Leishmania donovani develops resistance to drug combinations. PLoS Negl Trop Dis. 2012;6(12):e1974.
Hendrickx S, Guerin P, Caljon G, Croft S, Maes L. Evaluating drug resistance in visceral leishmaniasis: the challenges. Parasitology. 2018;145(4):453-463.
Murta SM, Gazzinelli RT, Brener Z, Romanha AJ. Molecular characterization of susceptible and naturally resistant strains of Trypanosoma cruzi to benznidazole and nifurtimox. Mol Biochem Parasitol. 1998;93(2):203-214.
Filardi L, Brener Z. Susceptibility and natural resistance of Trypanosoma cruzi strains to drugs used clinically in Chagas disease. Trans R Soc Trop Med Hyg. 1987;81(5):755-759.
Vinayak S, Pawlowic MC, Sateriale A, et al. Genetic modification of the diarrhoeal pathogen Cryptosporidium parvum. Nature. 2015;523(7561):477-480.
Werbovetz KA. Target-based drug discovery for malaria, leishmaniasis, and trypanosomiasis. Curr Med Chem. 2000;7(8):835-860.
Baden L, Katz J, Franck L, et al. Successful toxoplasmosis prophylaxis after orthotopic cardiac transplantation with trimethoprim-sulfamethoxazole1. Transplantation. 2003;75(3):339-343.
Glaser TA, Baatz JE, Kreishman GP, Mukkada AJ. pH homeostasis in Leishmania donovani amastigotes and promastigotes. Proc Natl Acad Sci. 1988;85(20):7602-7606.
Serrano-Martín X, Payares G, Mendoza-León A. Glibenclamide, a blocker of K+ ATP channels, shows antileishmanial activity in experimental murine cutaneous leishmaniasis. Antimicrob Agents Chemother. 2006;50(12):4214-4216.
Orué A, Pérez JL, Fuentes J, Odremán I, Serrano-Martín X, Mendoza-León A. Leishmania sp.: efecto de la glibenclamida, un bloqueador de canales de K+ ATP, sobre el ciclo de vida in vitro. Salus. 2007;11(1):32-36.
Marchesini N, Ruiz FA, Vieira M, Docampo R. Acidocalcisomes are functionally linked to the contractile vacuole of Dictyostelium discoideum. J Biol Chem. 2002;277(10):8146-8153.
Meade JC. P-type transport ATPases in Leishmania and Trypanosoma. Parasite. 2019;26:69.
Van Der Heyden N, Docampo R. Intracellular pH in mammalian stages of Trypanosoma cruzi is K+-dependent and regulated by H+-ATPases. Mol Biochem Parasitol. 2000;105(2):237-251.
Mondolfi AP, Stavropoulos C, Gelanew T, et al. Successful treatment of Old World cutaneous leishmaniasis caused by Leishmania infantum with posaconazole. Antimicrob Agents Chemother. 2011;55(4):1774-1776.
Lovett JL, Sibley LD. Intracellular calcium stores in Toxoplasma gondii govern invasion of host cells. J Cell Sci. 2003;116(14):3009-3016.
Carruthers VB, Moreno SN, Sibley DL. Ethanol and acetaldehyde elevate intracellular [Ca2+] and stimulate microneme discharge in Toxoplasma gondii. Biochem J. 1999;342(2):379-386.
Lovett JL, Marchesini N, Moreno SN, Sibley LD. Toxoplasma gondii microneme secretion involves intracellular Ca2+ release from inositol 1, 4, 5-triphosphate (IP3)/ryanodine-sensitive stores. J Biol Chem. 2002;277(29):25870-25876.
Del Carmen MG, Mondragon M, Gonzalez S, Mondragon R. Induction and regulation of conoid extrusion in Toxoplasma gondii. Cell Microbiol. 2009;11(6):967-982.
Vieira MC, Moreno SN. Mobilization of intracellular calcium upon attachment of Toxoplasma gondii tachyzoites to human fibroblasts is required for invasion. Mol Biochem Parasitol. 2000;106(1):157-162.
Pace DA, McKnight CA, Liu J, Jimenez V, Moreno SN. Calcium entry in Toxoplasma gondii and its enhancing effect of invasion-linked traits. J Biol Chem. 2014;289(28):19637-19647.
Pace DA, Moreno SN, Lourido S. Calcium storage and homeostasis in Toxoplasma gondii. Toxoplasma gondii. Cambridge, MA: Academic Press; 2020:547-575.
Wasserman M, Alarcón C, Mendoza PM. Effects of Ca++ depletion on the asexual cell cycle of Plasmodium falciparum. Am J Trop Med Hyg. 1982;31(4):711-717.
Zipprer EM, Neggers M, Kushwaha A, Rayavara K, Desai SA. A kinetic fluorescence assay reveals unusual features of Ca++ uptake in Plasmodium falciparum-infected erythrocytes. Malar J. 2014;13(1):184.
Glushakova S, Lizunov V, Blank PS, Melikov K, Humphrey G, Zimmerberg J. Cytoplasmic free Ca 2+ is essential for multiple steps in malaria parasite egress from infected erythrocytes. Malar J. 2013;12(1):41.
Garg S, Agarwal S, Kumar S, Yazdani SS, Chitnis CE, Singh S. Calcium-dependent permeabilization of erythrocytes by a perforin-like protein during egress of malaria parasites. Nat Commun. 2013;4(1):1-12.
Weiss GE, Gilson PR, Taechalertpaisarn T, et al. Revealing the sequence and resulting cellular morphology of receptor-ligand interactions during Plasmodium falciparum invasion of erythrocytes. PLoS Pathog. 2015;11(2):e1004670.
Fierro MA, Asady B, Brooks CF, et al. An endoplasmic reticulum CREC family protein regulates the egress proteolytic cascade in malaria parasites. mBio. 2020;11(1).
Anigboro AA, Avwioroko OJ, Cholu CO. Phytochemical constituents, antimalarial efficacy, and protective effect of Eucalyptus camaldulensis aqueous leaf extract in Plasmodium berghei-Infected Mice. Prev Nutr Food Sci. 2020;25(1):58-64.
Moreno SN, Docampo R. Calcium regulation in protozoan parasites. Curr Opin Microbiol. 2003;6(4):359-364.
Cheemadan S, Ramadoss R, Bozdech Z. Role of calcium signaling in the transcriptional regulation of the apicoplast genome of Plasmodium falciparum. BioMed Res Int. 2014;2014:1-12.
Rai P, Sharma D, Soni R, Khatoon N, Sharma B, Bhatt TK. Plasmodium falciparum apicoplast and its transcriptional regulation through calcium signaling. J Microbiol. 2017;55(4):231-236.
Kadian K, Gupta Y, Singh HV, Kempaiah P, Rawat M. Apicoplast metabolism: parasite's Achilles’ heel. Curr Top Med Chem. 2018;18(22):1987-1997.
Milton ME, Nelson SW. Replication and maintenance of the Plasmodium falciparum apicoplast genome. Mol Biochem Parasitol. 2016;208(2):56-64.
Philosoph H, Zilberstein D. Regulation of intracellular calcium in promastigotes of the human protozoan parasite Leishmania donovani. J Biol Chem. 1989;264(18):10420-10424.
Das R, Roy A, Dutta N, Majumder HK. Reactive oxygen species and imbalance of calcium homeostasis contributes to curcumin induced programmed cell death in Leishmania donovani. Apoptosis. 2008;13(7):867-882.
Chiurillo MA, Lander N, Vercesi AE, Docampo R. IP3 receptor-mediated Ca2+ release from acidocalcisomes regulates mitochondrial bioenergetics and prevents autophagy in Trypanosoma cruzi. Cell Calcium. 2020;92:102284.
Irigoín F, Inada NM, Fernandes MP, et al. Mitochondrial calcium overload triggers complement-dependent superoxide-mediated programmed cell death in Trypanosoma cruzi. Biochem J. 2009;418(3):595-604.
Docampo R, Vercesi AE, Huang G. Mitochondrial calcium transport in trypanosomes. Mol Biochem Parasitol. 2014;196(2):108-116.
Chiurillo MA, Lander N, Bertolini MS, Storey M, Vercesi AE, Docampo R. Different roles of mitochondrial calcium uniporter complex subunits in growth and infectivity of Trypanosoma cruzi. mBio. 2017;8(3):e00574-17.
Lander N, Chiurillo MA, Bertolini MS, Storey M, Vercesi AE, Docampo R. Calcium-sensitive pyruvate dehydrogenase phosphatase is required for energy metabolism, growth, differentiation, and infectivity of Trypanosoma cruzi. J Biol Chem. 2018;293(45):17402-17417.
Bowles DJ, Voorheis HP. Release of the surface coat from the plasma membrane of intact bloodstream forms of Trypanosoma brucei requires Ca2+. FEBS Lett. 1982;139(1):17-21.
Carruthers VB. Host cell invasion by the opportunistic pathogen Toxoplasma gondii. Acta Trop. 2002;81(2):111-122.
Carruthers VB, Sibley L. Sequential protein secretion from three distinct organelles of Toxoplasma gondii accompanies invasion of human fibroblasts. Eur J Cell Biol. 1997;73(2):114-123.
Lourido S, Moreno SN. The calcium signaling toolkit of the Apicomplexan parasites Toxoplasma gondii and Plasmodium spp. Cell Calcium. 2015;57(3):186-193.
Triana MAH, Márquez-Nogueras KM, Vella SA, Moreno SN. Calcium signaling and the lytic cycle of the Apicomplexan parasite Toxoplasma gondii. Biochim Biophys Acta BBA-Mol Cell Res. 2018;1865(11):1846-1856.
Ramakrishnan S, Docampo R. Membrane proteins in trypanosomatids involved in Ca2+ homeostasis and signaling. Genes. 2018;9(6):304.
Prole DL, Taylor CW. Identification of intracellular and plasma membrane calcium channel homologues in pathogenic parasites. PLoS One. 2011;6(10):e26218.
Chen X-M, O'Hara SP, Huang BQ, et al. Apical organelle discharge by Cryptosporidium parvum is temperature, cytoskeleton, and intracellular calcium dependent and required for host cell invasion. Infect Immun. 2004;72(12):6806-6816.
Sarkhosh T, Zhang XF, Jellison KL, Jedlicka SS. Calcium-mediated biophysical binding of Cryptosporidium parvum oocysts to surfaces is sensitive to oocyst age. Appl Environ Microbiol. 2019;85(17):e00816-e00819.
Luo X, Jedlicka S, Jellison K. Pseudo-second-order calcium-mediated Cryptosporidium parvum oocyst attachment to environmental biofilms. Appl Env Microbiol. 2017;83(1):e02339-16.
Docampo R, Huang G. Calcium signaling in trypanosomatid parasites. Cell Calcium. 2015;57(3):194-202.
Benaim G, García-Marchán Y, Reyes C, Uzcanga G, Figarella K. Identification of a sphingosine-sensitive Ca2+ channel in the plasma membrane of Leishmania mexicana. Biochem Biophys Res Commun. 2013;430(3):1091-1096.
Rodriguez-Duran J, Pinto-Martinez A, Castillo C, Benaim G. Identification and electrophysiological properties of a sphingosine-dependent plasma membrane Ca2+ channel in Trypanosoma cruzi. FEBS J. 2019;286(19):3909-3925.
Patel S, Cai X. Evolution of acidic Ca2+ stores and their resident Ca2+-permeable channels. Cell Calcium. 2015;57(3):222-230.
Rotmann A, Sanchez C, Guiguemde A, et al. PfCHA is a mitochondrial divalent cation/H+ antiporter in Plasmodium falciparum. Mol Microbiol. 2010;76(6):1591-1606.
RS Garcia C, Alves E, HS Pereira P, et al. InsP3 signaling in apicomplexan parasites. Curr Top Med Chem. 2017;17(19):2158-2165.
Nagamune K, Sibley LD. Comparative genomic and phylogenetic analyses of calcium ATPases and calcium-regulated proteins in the apicomplexa. Mol Biol Evol. 2006;23(8):1613-1627.
Aurrecoechea C, Barreto A, Basenko EY, et al. EuPathDB: the eukaryotic pathogen genomics database resource. Nucleic Acids Res. 2017;45(D1):D581-D591.
Kanehisa M, Furumichi M, Tanabe M, Sato Y, Morishima K. KEGG: new perspectives on genomes, pathways, diseases and drugs. Nucleic Acids Res. 2017;45(D1):D353-D361.
Yuan S, Chan HS, Filipek S. Vogel H. PyMOL and Inkscape bridge the data and the data visualization. Structure. 2016;24(12):2041-2042.
Sanderson T, Rayner JC. PhenoPlasm: a database of disruption phenotypes for malaria parasite genes. Wellcome Open Res. 2017;2:45.
Janse CJ, Kroeze H, van Wigcheren A, et al. A genotype and phenotype database of genetically modified malaria-parasites. Trends Parasitol. 2011;27(1):31-39.
Urán Landaburu L, Berenstein AJ, Videla S, et al. TDR Targets 6: driving drug discovery for human pathogens through intensive chemogenomic data integration. Nucleic Acids Res. 2020;48(D1):D992-D1005.
Agüero F, Al-Lazikani B, Aslett M, et al. Genomic-scale prioritization of drug targets: the TDR Targets database. Nat Rev Drug Discov. 2008;7(11):900-907.
Magariños MP, Carmona SJ, Crowther GJ, et al. TDR Targets: a chemogenomics resource for neglected diseases. Nucleic Acids Res. 2012;40(D1):D1118-D1127.
Thomas P, Sedillo J, Oberstaller J, et al. Phenotypic screens identify parasite genetic factors associated with malarial fever response in Plasmodium falciparum piggyBac mutants. mSphere. 2016;1(5):e00273-16.
Sidik SM, Huet D, Ganesan SM, et al. A genome-wide CRISPR screen in Toxoplasma identifies essential apicomplexan genes. Cell. 2016;166(6):1423-1435.
Siegel TN, Hekstra DR, Wang X, Dewell S, Cross GA. Genome-wide analysis of mRNA abundance in two life-cycle stages of Trypanosoma brucei and identification of splicing and polyadenylation sites. Nucleic Acids Res. 2010;38(15):4946-4957.
Schwach Frank, Bushell Ellen, Gomes Ana Rita, Anar Burcu, Girling Gareth, Herd Colin, Rayner Julian C., Billker Oliver. PlasmoGEM, a database supporting a community resource for large-scale experimental genetics in malaria parasites. Nucleic Acids Research. 2015;43 (D1):D1176-D1182. http://dx.doi.org/10.1093/nar/gku1143
Bushell E, Gomes AR, Sanderson T, et al. Functional profiling of a Plasmodium genome reveals an abundance of essential genes. Cell. 2017;170(2):260-272.
Alsford S, Turner DJ, Obado SO, et al. High-throughput phenotyping using parallel sequencing of RNA interference targets in the African trypanosome. Genome Res. 2011;21(6):915-924.
Lourido S, Shuman J, Zhang C, Shokat KM, Hui R, Sibley LD. Calcium-dependent protein kinase 1 is an essential regulator of exocytosis in Toxoplasma. Nature. 2010;465(7296):359-362.
Stevens FC. Calmodulin: an introduction. Can J Biochem Cell Biol. 1983;61(8):906-910.
Chin D, Means AR. Calmodulin: a prototypical calcium sensor. Trends Cell Biol. 2000;10(8):322-328.
Elíes J, Yáñez M, Pereira TM, Gil-Longo J, MacDougall DA, Campos-Toimil M. An Update to Calcium Binding Proteins. Calcium Signaling. Advances in Experimental Medicine and Biology. Cham: Springer; 2020:183-213.
Matsumoto Y, Perry G, Scheibel L, Aikawa M. Role of calmodulin in Plasmodium falciparum: implications for erythrocyte invasion by the merozoite. Eur J Cell Biol. 1987;45(1):36-43.
Sunter JD, Yanase R, Wang Z, et al. Leishmania flagellum attachment zone is critical for flagellar pocket shape, development in the sand fly, and pathogenicity in the host. Proc Natl Acad Sci. 2019;116(13):6351-6360.
Mukhopadhyay AG, Dey CS. Role of calmodulin and calcineurin in regulating flagellar motility and wave polarity in Leishmania. Parasitol Res. 2017;116(11):3221-3228.
Orr GA, Tanowitz HB, Wittner M. Trypanosoma cruzi: stage expression of calmodulin-binding proteins. Exp Parasitol. 1992;74(2):127-133.
Polonais V, Javier Foth B, Chinthalapudi K, et al. Unusual anchor of a motor complex (MyoD-MLC2) to the plasma membrane of Toxoplasma gondii. Traffic. 2011;12(3):287-300.
Long S, Brown KM, Drewry LL, Anthony B, Phan IQ, Sibley LD. Calmodulin-like proteins localized to the conoid regulate motility and cell invasion by Toxoplasma gondii. PLoS Pathog. 2017;13(5):e1006379.
Lourido S, Tang K, Sibley LD. Distinct signalling pathways control Toxoplasma egress and host-cell invasion. EMBO J. 2012;31(24):4524-4534.
Artz JD, Wernimont AK, Allali-Hassani A, et al. The Cryptosporidium parvum kinome. BMC Genomics. 2011;12(1):478.
Kashif M, P Manna P, Akhter Y, Alaidarous M, Rub A. Screening of novel inhibitors against Leishmania donovani calcium ion channel to fight leishmaniasis. Infect Disord-Drug Targets Former Curr Drug Targets-Infect Disord. 2017;17(2):120-129.
Moreno SN, Zhong L. Acidocalcisomes in Toxoplasma gondii tachyzoites. Biochem J. 1996;313(2):655-659.
Pinto-Martinez A, Hernández-Rodríguez V, Rodríguez-Durán J, Hejchman E, Benaim G. Anti-Trypanosoma cruzi action of a new benzofuran derivative based on amiodarone structure. Exp Parasitol. 2018;189 1898-15.
Tempone AG, Taniwaki NN, Reimão JQ. Antileishmanial activity and ultrastructural alterations of Leishmania (L.) chagasi treated with the calcium channel blocker nimodipine. Parasitol Res. 2009;105(2):499-505.
Reimão JQ, Colombo FA, Pereira-Chioccola VL, Tempone AG. In vitro and experimental therapeutic studies of the calcium channel blocker bepridil: detection of viable Leishmania (L.) chagasi by real-time PCR. Exp Parasitol. 2011;128(2):111-115.
Zhu G, Keithly JS. Molecular analysis of a P-type ATPase from Cryptosporidium parvum. Mol Biochem Parasitol. 1997;90(1):307-316.
Lendner M, Daugschies A. Cryptosporidium infections: molecular advances. Parasitology. 2014;141(11):1511-1532.
Mishina YV, Krishna S, Haynes RK, Meade JC. Artemisinins inhibit Trypanosoma cruzi and Trypanosoma brucei rhodesiense in vitro growth. Antimicrob Agents Chemother. 2007;51(5):1852-1854.
Cardi D, Pozza A, Arnou B, et al. Purified E255L mutant SERCA1a and purified PfATP6 are sensitive to SERCA-type inhibitors but insensitive to artemisinins. J Biol Chem. 2010;285(34):26406-26416.
Feng J, Kong X, Xu D, et al. Investigation and evaluation of genetic diversity of Plasmodium falciparum Kelch 13 polymorphisms imported from Southeast Asia and Africa in Southern China. Front Public Health. 2019;7.
Cui L, Wang Z, Jiang H, et al. Lack of association of the S769N mutation in Plasmodium falciparum SERCA (PfATP6) with resistance to artemisinins. Antimicrob Agents Chemother. 2012;56(5):2546-2552.
Lu H-G, Zhong L, Chang K-P, Docampo R. Intracellular Ca2+ pool content and signaling and expression of a calcium pump are linked to virulence in Leishmania mexicana amazonesis amastigotes. J Biol Chem. 1997;272(14):9464-9473.
Subramaniam S, Schmid CD, Guan XL, Mäser P. Using yeast synthetic lethality to inform drug combination for malaria. Antimicrob Agents Chemother. 2018;62(4):e01533-17.
Zhang R, Suwanarusk R, Malleret B, et al. A basis for rapid clearance of circulating ring-stage malaria parasites by the spiroindolone KAE609. J Infect Dis. 2016;213(1):100-104.
Bouwman SA, Zoleko-Manego R, Renner KC, Schmitt EK, Mombo-Ngoma G, Grobusch MP. The early preclinical and clinical development of cipargamin (KAE609), a novel antimalarial compound. Travel Med Infect Dis. 2020;36:36101765.
Gaur AH, McCarthy JS, Panetta JC. Safety, tolerability, pharmacokinetics, and antimalarial efficacy of a novel Plasmodium falciparum ATP4 inhibitor SJ733: a first-in-human and induced blood-stage malaria phase 1a/b trial. Lancet Infect Dis. 2020;8:964-975.
França-Botelho AC, França JL, Oliveira FM, et al. Melatonin reduces the severity of experimental amoebiasis. Parasit Vectors. 2011;4(1):62.
Avunduk AM, Avunduk MC, Baltacı AK, Moğulkoç R. Effect of melatonin and zinc on the immune response in experimental Toxoplasma retinochoroiditis. Ophthalmologica. 2007;221(6):421-425.
Koyama FC, Ribeiro RY, Garcia JL, Azevedo MF, Chakrabarti D, Garcia CR. Ubiquitin proteasome system and the atypical kinase PfPK7 are involved in melatonin signaling in Plasmodium falciparum. J Pineal Res. 2012;53(2):147-153.
Alves E, Bartlett PJ, Garcia CR, Thomas AP. Melatonin and IP3-induced Ca2+ release from intracellular stores in the malaria parasite Plasmodium falciparum within infected red blood cells. J Biol Chem. 2011;286(7):5905-5912.
Pinazo M-J, Espinosa G, Gállego M, López-Chejade PL, Urbina JA, Gascón J. Successful treatment with posaconazole of a patient with chronic Chagas disease and systemic lupus erythematosus. Am J Trop Med Hyg. 2010;82(4):583-587.
Benaim G, Sanders JM, Garcia-Marchán Y, et al. Amiodarone has intrinsic anti-Trypanosoma c ruzi activity and acts synergistically with posaconazole. J Med Chem. 2006;49(3):892-899.
Lebsack A, Lebsack AD, Gunzner J, et al. Identification and synthesis of [1, 2, 4] triazolo [3, 4-a] phthalazine derivatives as high-affinity ligands to the α2δ-1 subunit of voltage gated calcium channel. Bioorg Med Chem Lett. 2004;14(10):2463-2467.
Figarella K, Marsiccobetre S, Arocha I, et al. Ergosterone-coupled Triazol molecules trigger mitochondrial dysfunction, oxidative stress, and acidocalcisomal Ca2+ release in Leishmania mexicana promastigotes. Microb Cell. 2016;3(1):14-28.
Reimão JQ, Scotti MT, Tempone AG. Anti-leishmanial and anti-trypanosomal activities of 1, 4-dihydropyridines: in vitro evaluation and structure-activity relationship study. Bioorg Med Chem. 2010;18(22):8044-8053.
Shtutin V, Weiss LM, Morris SA, et al. Effects of early and late verapamil administration on the development of cardiomyopathy in experimental chronic Trypanosoma cruzi (Brazil strain) infection. Parasitol Res. 2004;92(6):496-501.
Masseno V, Muriithi S, Nzila A. In vitro chemosensitization of Plasmodium falciparum to antimalarials by verapamil and probenecid. Antimicrob Agents Chemother. 2009;53(7):3131-3134.
Shokri A, Sharifi I, Khamesipour A, et al. The effect of verapamil on in vitro susceptibility of promastigote and amastigote stages of Leishmania tropica to meglumine antimoniate. Parasitol Res. 2012;110(3):1113-1117.
Coelho AC, Gentil LG, da Silveira JF, Cotrim PC. Characterization of Leishmania (Leishmania) amazonensis promastigotes resistant to pentamidine. Exp Parasitol. 2008;120(1):98-102.
Neal R, van Bueren J, McCoy NG, Iwobi M. Reversal of drug resistance in Trypanosoma cruzi and Leishmania donovani by verapamil. Trans R Soc Trop Med Hyg. 1989;83(2):197-198.
Benaim G, Paniz-Mondolfi AE, Sordillo EM, Martinez-Sotillo N. Disruption of intracellular calcium homeostasis as a therapeutic target against Trypanosoma cruzi. Front Cell Infect Microbiol. 2020;10:1046.
Wirjanata G, Handayuni I, Prayoga P, et al. Plasmodium falciparum and Plasmodium vivax demonstrate contrasting chloroquine resistance reversal phenotypes. Antimicrob Agents Chemother. 2017;61(8):e00355-17.