title: Expression of cytosolic peroxiredoxins in Plasmodium berghei ookinetes is regulated by environmental factors in the mosquito bloodmeal.
abstract: The Plasmodium ookinete develops over several hours in the bloodmeal of its mosquito vector where it is exposed to exogenous stresses, including cytotoxic reactive oxygen species (ROS). How the parasite adapts to these challenging conditions is not well understood. We have systematically investigated the expression of three cytosolic antioxidant proteins, thioredoxin-1 (Trx-1), peroxiredoxin-1 (TPx-1), and 1-Cys peroxiredoxin (1-Cys Prx), in developing ookinetes of the rodent parasite Plasmodium berghei under various growth conditions. Transcriptional profiling showed that tpx-1 and 1-cys prx but not trx-1 are more strongly upregulated in ookinetes developing in the mosquito bloodmeal when compared to ookinetes growing under culture conditions. Confocal immunofluorescence imaging revealed comparable expression patterns on the corresponding proteins. 1-Cys Prx in particular exhibited strong expression in mosquito-derived ookinetes but was not detectable in cultured ookinetes. Furthermore, ookinetes growing in culture upregulated tpx-1 and 1-cys prx when challenged with exogenous ROS in a dose-dependent fashion. This suggests that environmental factors in the mosquito bloodmeal induce upregulation of cytosolic antioxidant proteins in Plasmodium ookinetes. We found that in a parasite line lacking TPx-1 (TPx-1KO), expression of 1-Cys Prx occurred significantly earlier in mosquito-derived TPx-1KO ookinetes when compared to wild type (WT) ookinetes. The protein was also readily detectable in cultured TPx-1KO ookinetes, indicating that 1-Cys Prx at least in part compensates for the loss of TPx-1 in vivo. We hypothesize that this dynamic expression of the cytosolic peroxiredoxins reflects the capacity of the developing Plasmodium ookinete to rapidly adapt to the changing conditions in the mosquito bloodmeal. This would significantly increase its chances of survival, maturation and subsequent escape. Our results also emphasize that environmental conditions must be taken into account when investigating Plasmodium-mosquito interactions.
authors: Department of Biology, Loyola University Chicago, Chicago, Illinois, United States of America.
authors: Benjamin A
authors: BA
authors: Turturice
authors: Michael A
authors: MA
authors: Lamm
authors: James J
authors: JJ
authors: Tasch
authors: Angelika
authors: A
authors: Zalewski
authors: Rachel
authors: R
authors: Kooistra
authors: Eric H
authors: EH
authors: Schroeter
authors: Sapna
authors: S
authors: Sharma
authors: Shin-Ichiro
authors: S
authors: Kawazu
authors: Stefan M
authors: SM
authors: Kanzok
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001769:Blood; D002478:Cells, Cultured; D009033:Culicidae / Q000469:parasitology*; D003600:Cytosol / Q000201:enzymology*; D005247:Feeding Behavior; D006790:Host-Parasite Interactions; D007303:Insect Vectors / Q000469:parasitology; D008288:Malaria; D033661:Oocysts / Q000201:enzymology*; D054464:Peroxiredoxins / Q000378:metabolism*; D010962:Plasmodium berghei / Q000201:enzymology / Q000472:pathogenicity*; D017382:Reactive Oxygen Species; D013879:Thioredoxins / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D000975:Antioxidants; D017382:Reactive Oxygen Species; D013879:Thioredoxins; D054464:Peroxiredoxins
references: Mol Biochem Parasitol. 2000 Jul;109(2):165-9
references: 10960175
references: Free Radic Biol Med. 2005 Jun 15;38(12):1543-52
references: 15917183
references: Int J Parasitol. 2003 Aug;33(9):933-43
references: 12906877
references: PLoS Pathog. 2011 Mar;7(3):e1001320
references: 21445237
references: J Biol Chem. 2012 Feb 10;287(7):4403-10
references: 22147704
references: Nature. 1998 Mar 19;392(6673):289-92
references: 9521324
references: Parasit Vectors. 2009 Jul 15;2(1):32
references: 19604379
references: J Biol Chem. 2007 Oct 26;282(43):31429-36
references: 17720812
references: Nature. 2002 Oct 3;419(6906):498-511
references: 12368864
references: Antioxid Redox Signal. 2006 Jul-Aug;8(7-8):1227-39
references: 16910770
references: Parasitol Int. 2008 Mar;57(1):1-7
references: 17890140
references: Parasitol Int. 2010 Jun;59(2):298-302
references: 20307687
references: Redox Rep. 2003;8(5):246-50
references: 14962358
references: Mol Microbiol. 2006 Aug;61(4):948-59
references: 16879648
references: J Biol Chem. 1988 Feb 5;263(4):1910-4
references: 2828357
references: PLoS Pathog. 2010 Dec 23;6(12):e1001242
references: 21203490
references: Mol Biochem Parasitol. 2001 Apr 6;113(2):303-8
references: 11295184
references: FEBS Lett. 2003 Jul 17;547(1-3):140-4
references: 12860402
references: Mol Biochem Parasitol. 2001 Aug;116(1):73-9
references: 11463468
references: Biochem Soc Trans. 1996 Feb;24(1):67-72
references: 8674743
references: Malar J. 2004 Jul 09;3:23
references: 15245577
references: Mol Microbiol. 2004 Sep;53(5):1291-305
references: 15387810
references: Parasitol Int. 2005 Mar;54(1):35-41
references: 15710548
references: Subcell Biochem. 2007;44:219-29
references: 18084896
references: Free Radic Res Commun. 1991;12-13 Pt 1:137-46
references: 1649081
references: Int J Parasitol. 2003 Nov;33(13):1455-61
references: 14572508
references: Science. 2005 Jan 7;307(5706):82-6
references: 15637271
references: J Biol Chem. 2000 Dec 22;275(51):40180-6
references: 11013257
references: EMBO J. 2000 Nov 15;19(22):6030-40
references: 11080150
references: Proc Natl Acad Sci U S A. 1998 May 12;95(10):5700-5
references: 9576947
references: Int J Parasitol. 2012 May 15;42(6):519-27
references: 22406332
references: Parasit Vectors. 2012 Nov 12;5:252
references: 23146411
references: Proteomics. 2008 Jun;8(12):2492-9
references: 18563747
references: Malar J. 2009 May 29;8:113
references: 19480682
references: Mol Biochem Parasitol. 2008 Jun;159(2):142-5
references: 18417228
references: PLoS Pathog. 2010 Feb 12;6(2):e1000767
references: 20169188
references: Mol Biochem Parasitol. 2006 Jul;148(1):44-51
references: 16597467
references: J Mol Biol. 2007 Jan 26;365(4):1033-46
references: 17098255
references: PLoS Pathog. 2009 Apr;5(4):e1000383
references: 19360125
references: Mol Biol Cell. 2000 Dec;11(12):4241-57
references: 11102521
references: Free Radic Biol Med. 2007 Jan 1;42(1):132-42
references: 17157200
references: J Biol Chem. 2008 Feb 8;283(6):3217-3223
references: 18065421
references: Mol Microbiol. 1999 Jan;31(1):253-60
references: 9987126
references: J Biol Chem. 2001 Mar 9;276(10):7397-403
references: 11087748
references: J Parasitol. 2002 Aug;88(4):702-6
references: 12197117
references: J Biol Chem. 2011 Apr 1;286(13):11746-55
references: 21282103
references: Infect Immun. 2001 Aug;69(8):5064-71
references: 11447187
references: BMC Bioinformatics. 2011;12 Suppl 13:S3
references: 22373214
references: Eur J Biochem. 2001 Mar;268(5):1404-9
references: 11231293
references: Exp Parasitol. 2002 May;101(1):73-6
references: 12243741
references: Mol Biochem Parasitol. 2003 Aug 31;130(2):75-81
references: 12946843
references: FEBS J. 2005 Apr;272(7):1784-91
references: 15794764
references: Science. 2006 Aug 4;313(5787):667-9
references: 16888139
references: FEBS J. 2012 Oct;279(20):3872-88
references: 22889167
references: Dev Comp Immunol. 2010 Apr;34(4):387-95
references: 20026176