title: Parasite maturation and host serum iron influence the labile iron pool of erythrocyte stage Plasmodium falciparum.
abstract: Iron is a critical and tightly regulated nutrient for both the malaria parasite and its human host. The importance of the relationship between host iron and the parasite has been underscored recently by studies showing that host iron supplementation may increase the risk of falciparum malaria. It is unclear what host iron sources the parasite is able to access. We developed a flow cytometry-based method for measuring the labile iron pool (LIP) of parasitized erythrocytes using the nucleic acid dye STYO 61 and the iron sensitive dye, calcein acetoxymethyl ester (CA-AM). This new approach enabled us to measure the LIP of P. falciparum through the course of its erythrocytic life cycle and in response to the addition of host serum iron sources. We found that the LIP increases as the malaria parasite develops from early ring to late schizont stage, and that the addition of either transferrin or ferric citrate to culture media increases the LIP of trophozoites. Our method for detecting the LIP within malaria parasitized RBCs provides evidence that the parasite is able to access serum iron sources as part of the host vs. parasite arms race for iron.
authors: Department of Microbiology and Immunology, University of North Carolina-Chapel Hill, Chapel Hill, USA, United States.
authors: Martha
authors: M
authors: Clark
authors: Nancy C
authors: NC
authors: Fisher
authors: Raj
authors: R
authors: Kasthuri
authors: Carla
authors: C
authors: Cerami Hand
mesh_terms: D004912:Erythrocytes / Q000378:metabolism* / Q000469:parasitology; D006790:Host-Parasite Interactions; D006801:Humans; D007501:Iron / Q000378:metabolism*; D016778:Malaria, Falciparum / Q000378:metabolism*; D010963:Plasmodium falciparum / Q000502:physiology*; D052939:Schizonts / Q000378:metabolism
chemical_list: D007501:Iron
references: Curr Top Microbiol Immunol. 2005;295:293-324
references: 16265896
references: Malar J. 2003 May 7;2:11
references: 12801422
references: PLoS Pathog. 2010 Aug 12;6(8):e1000949
references: 20711357
references: J Infect Dis. 1997 Jan;175(1):226-30
references: 8985227
references: Cytometry A. 2010 Mar;77(3):253-63
references: 20091670
references: Mol Biochem Parasitol. 1999 Jun 25;101(1-2):43-59
references: 10413042
references: Anal Biochem. 1997 May 15;248(1):31-40
references: 9177722
references: Ann Nutr Metab. 2012;60(2):98-107
references: 22398912
references: Proc Natl Acad Sci U S A. 1986 Nov;83(22):8565-9
references: 3534892
references: J Parasitol. 1982 Dec;68(6):1068-71
references: 6757398
references: J Cell Sci. 2006 Mar 15;119(Pt 6):1016-25
references: 16492710
references: Nature. 1991 Sep 5;353(6339):73-5
references: 1715521
references: Ann Trop Paediatr. 1989 Mar;9(1):17-23
references: 2471438
references: Lancet. 1975 Mar 22;1(7908):653-4
references: 47080
references: Br J Haematol. 2008 Jun;142(2):301-7
references: 18503586
references: Chem Biol. 2012 Jun 22;19(6):731-41
references: 22726687
references: FEBS Lett. 1996 Mar 18;382(3):304-8
references: 8605990
references: Lancet. 2006 Jan 14;367(9505):133-43
references: 16413877
references: Blood. 2008 Aug 1;112(3):866-74
references: 18369153
references: J Nutr. 2001 Feb;131(2S-2):616S-633S; discussion 633S-635S
references: 11160594
references: J Infect Dis. 2001 May 1;183(9):1388-94
references: 11294671
references: Mol Biochem Parasitol. 1992 Oct;55(1-2):9-20
references: 1435878
references: J Biol Chem. 2012 Nov 2;287(45):37793-807
references: 22992734
references: Am J Physiol. 1995 Jun;268(6 Pt 1):C1354-61
references: 7611353
references: J Exp Med. 1988 Jul 1;168(1):375-87
references: 3294334
references: J Exp Med. 1996 Sep 1;184(3):945-54
references: 9064354
references: Annu Rev Neurosci. 1989;12:227-53
references: 2648950
references: Cell. 2011 May 27;145(5):665-77
references: 21620134
references: Biochem J. 2007 Apr 15;403(2):261-6
references: 17233627
references: J Biol Chem. 1995 Oct 13;270(41):24209-15
references: 7592626
references: Nature. 1986 Nov 27-Dec 3;324(6095):388-91
references: 3097554
references: PLoS One. 2012;7(5):e37171
references: 22629364
references: Cytometry A. 2008 Jan;73(1):22-7
references: 18044720
references: N Engl J Med. 1992 Nov 19;327(21):1473-7
references: 1406879
references: Proc Natl Acad Sci U S A. 2010 Aug 10;107(32):14378-83
references: 20660744
references: Br J Haematol. 1984 Oct;58(2):289-93
references: 6383456
references: J Intern Med. 1989 Nov;226(5):349-55
references: 2681511
references: Cell Microbiol. 2007 Sep;9(9):2126-40
references: 17466014