title: Chloroquine has a cytotoxic effect on Acanthamoeba encystation through modulation of autophagy.
abstract: Encystation of Acanthamoeba castellanii is associated with resistance to chemotherapeutic agents. Blocking the encystation process could potentiate the efficacy of chemotherapeutic agents and biocides. During encystation, autophagy is highly stimulated and required for proper encystation of Acanthamoeba. In this study, the cytotoxic effect of chloroquine, a well-known autophagy-inhibitory drug, was tested in A. castellanii. Chloroquine was able to selectively reduce cell survival during the encystation of A. castellanii. However, A. castellanii trophozoites and mature cysts were resistant to chloroquine. Chloroquine treatment led to an increase in the number and size of lysosomes in encysting cells. Moreover, chloroquine inhibited the degradation of long-lived proteins in the encysting cells. Decreased autophagic flux, indicated by an increased number of lysosomes and decreased degradation of long-lived proteins, may be the mechanism by which cell death is induced by chloroquine in encysting Acanthamoeba. These results suggest a potential novel therapeutic application of chloroquine as an anti-Acanthamoeba drug. Our findings also suggest that targeting autophagy could be a therapeutic strategy against Acanthamoeba infection.
authors.affiliation: Department of Microbiology, Keimyung University School of Medicine, Daegu, Republic of Korea.
authors.forename: Bijay Kumar
authors.initials: BK
authors.lastname: Jha
authors.affiliation: Department of Microbiology, Keimyung University School of Medicine, Daegu, Republic of Korea.
authors.forename: Hui-Jung
authors.initials: HJ
authors.lastname: Jung
authors.affiliation: Department of Microbiology, Keimyung University School of Medicine, Daegu, Republic of Korea.
authors.forename: Incheol
authors.initials: I
authors.lastname: Seo
authors.affiliation: Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Republic of Korea.
authors.forename: Hyun Ah
authors.initials: HA
authors.lastname: Kim
authors.affiliation: Department of Microbiology, Keimyung University School of Medicine, Daegu, Republic of Korea.
authors.forename: Seong-Il
authors.initials: SI
authors.lastname: Suh
authors.affiliation: Department of Microbiology, Keimyung University School of Medicine, Daegu, Republic of Korea.
authors.forename: Min-Ho
authors.initials: MH
authors.lastname: Suh
authors.affiliation: Department of Microbiology, Keimyung University School of Medicine, Daegu, Republic of Korea wonki@dsmc.or.kr.
authors.forename: Won-Ki
authors.initials: WK
authors.lastname: Baek
mesh_terms: D000048:Acanthamoeba / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D002738:Chloroquine / Q000494:pharmacology*; D004202:Disinfectants / Q000494:pharmacology*
chemical_list: D004202:Disinfectants; D002738:Chloroquine
references.citation: Clin Microbiol Rev. 2003 Apr;16(2):273-307
references.pmid: 12692099
references.citation: Southeast Asian J Trop Med Public Health. 1996 Jun;27(2):319-24
references.pmid: 9279996
references.citation: Br Med J. 1953 Apr 11;1(4814):811-3
references.pmid: 13032509
references.citation: J Cell Biol. 1969 Jun;41(3):786-805
references.pmid: 5768875
references.citation: Mol Biochem Parasitol. 2012 Jun;183(2):158-65
references.pmid: 22426571
references.citation: PLoS One. 2013;8(4):e60579
references.pmid: 23577127
references.citation: Pharmacol Rev. 2006 Mar;58(1):32-45
references.pmid: 16507881
references.citation: Neuro Oncol. 2010 May;12(5):473-81
references.pmid: 20406898
references.citation: Gastroenterology. 1975 Jul;69(1):35-41
references.pmid: 168120
references.citation: Braz J Infect Dis. 2010 Jul-Aug;14(4):372-3
references.pmid: 20963322
references.citation: Korean J Parasitol. 2011 Jun;49(2):103-8
references.pmid: 21738264
references.citation: Graefes Arch Clin Exp Ophthalmol. 2013 Sep;251(9):2111-7
references.pmid: 23686225
references.citation: Cell Biosci. 2011 Mar 08;1(1):10
references.pmid: 21711726
references.citation: Curr Opin Cell Biol. 2010 Apr;22(2):124-31
references.pmid: 20034776
references.citation: Eukaryot Cell. 2008 Mar;7(3):509-17
references.pmid: 18223117
references.citation: Clin Pharmacokinet. 1996 Oct;31(4):257-74
references.pmid: 8896943
references.citation: Drug Resist Updat. 2004 Feb;7(1):41-51
references.pmid: 15072770
references.citation: Exp Parasitol. 2012 Dec;132(4):524-9
references.pmid: 22878047
references.citation: J Ophthalmol. 2012;2012:484892
references.pmid: 23304449
references.citation: J Antimicrob Chemother. 2007 Jan;59(1):122-4
references.pmid: 17079240
references.citation: Mol Biochem Parasitol. 2009 Nov;168(1):43-8
references.pmid: 19560492
references.citation: Proc Natl Acad Sci U S A. 1978 Jul;75(7):3327-31
references.pmid: 28524
references.citation: Invest Ophthalmol Vis Sci. 2013 Sep 27;54(9):6363-72
references.pmid: 23900604
references.citation: Parasitol Res. 2012 Jul;111(1):1-6
references.pmid: 22411634
references.citation: Eukaryot Cell. 2013 Apr;12(4):567-74
references.pmid: 23397569
references.citation: J Biol Chem. 1996 Nov 8;271(45):28593-600
references.pmid: 8910489
references.citation: Eur J Pharmacol. 2009 Dec 25;625(1-3):220-33
references.pmid: 19836374
references.citation: Antimicrob Agents Chemother. 2014;58(3):1523-8
references.pmid: 24366747
references.citation: Am J Trop Med Hyg. 2012 Oct;87(4):715-8
references.pmid: 22869634
references.citation: PLoS One. 2011;6(9):e22876
references.pmid: 21909398
references.citation: Eukaryot Cell. 2008 Sep;7(9):1513-7
references.pmid: 18676958
references.citation: Cell. 2010 Feb 5;140(3):313-26
references.pmid: 20144757
references.citation: Science. 2004 Nov 5;306(5698):990-5
references.pmid: 15528435
references.citation: J Clin Microbiol. 2000 Oct;38(10):3892-5
references.pmid: 11015431
references.citation: Emerg Infect Dis. 2008 Nov;14(11):1743-6
references.pmid: 18976559
references.citation: Cell Res. 2010 Jul;20(7):748-62
references.pmid: 20548331
references.citation: J Gen Microbiol. 1974 Nov;85(1):139-45
references.pmid: 4436650
references.citation: Clin Infect Dis. 2002 Aug 15;35(4):434-41
references.pmid: 12145728
references.citation: Am J Ophthalmol. 2010 Jan;149(1):66-9
references.pmid: 19875089
references.citation: Korean J Parasitol. 2007 Dec;45(4):283-5
references.pmid: 18165710
references.citation: J Antimicrob Chemother. 2000 Jul;46(1):27-34
references.pmid: 10882685
references.citation: Ann Clin Microbiol Antimicrob. 2004 Dec 21;3:27
references.pmid: 15610563
references.citation: Biol Pharm Bull. 2005 Jun;28(6):947-51
references.pmid: 15930724
references.citation: J Eukaryot Microbiol. 2001 Jan-Feb;48(1):11-6
references.pmid: 11249185
references.citation: Invest Ophthalmol Vis Sci. 2010 Nov;51(11):6030-7
references.pmid: 20574031
references.citation: Mol Biochem Parasitol. 2012 Oct;185(2):121-6
references.pmid: 22917557
references.citation: J Neurochem. 2003 Mar;84(6):1266-74
references.pmid: 12614327
references.citation: FEMS Immunol Med Microbiol. 2007 Jun;50(1):1-26
references.pmid: 17428307
references.citation: Curr Treat Options Gastroenterol. 1999 Apr;2(2):97-103
references.pmid: 11096579
references.citation: Proc Natl Acad Sci U S A. 2010 Aug 10;107(32):14333-8
references.pmid: 20660757
references.citation: FEMS Microbiol Rev. 2006 Jul;30(4):564-95
references.pmid: 16774587
references.citation: Biochim Biophys Acta. 1998 May 29;1398(1):47-56
references.pmid: 9602053
references.citation: Methods Enzymol. 2009;452:47-61
references.pmid: 19200875
references.citation: Case Rep Ophthalmol Med. 2013;2013:608253
references.pmid: 24455365