Deletion of mitogen-activated protein kinase 1 inhibits development and growth of Toxoplasma gondii

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• 作者：Lili Cao ; Zedong Wang ; Shuchao Wang ; Jiping Li ; Xinglong Wang…
• 关键词：Toxoplasma gondii ; Mitogen ; activated protein kinase ; Asexual development ; Growth
• 刊名：Parasitology Research
• 出版年：2016
• 出版时间：February 2016
• 年：2016
• 卷：115
• 期：2
• 页码：797-805
• 全文大小：1,426 KB
• 参考文献：Anderson MZ, Brewer J, Singh U, Boothroyd JC (2009) A pseudouridine synthase homologue is critical to cellular differentiation in Toxoplasma gondii. Eukaryot Cell 8:398–409PubMedCentral CrossRef PubMed
  Belozerov VE, Lin ZY, Gingras AC, McDermott JC, Michael Siu KW (2012) High-resolution protein interaction map of the Drosophila melanogaster p38 mitogen-activated protein kinases reveals limited functional redundancy. Mol Cell Biol 32:3695–3706PubMedCentral CrossRef PubMed
  Bengs F, Scholz A, Kuhn D, Wiese M (2005) LmxMPK9, a mitogen-activated protein kinase homologue affects flagellar length in Leishmania mexicana. Mol Microbiol 55:1606–1615CrossRef PubMed
  Brumlik MJ, Pandeswara S, Ludwig SM, Jeansonne DP, Lacey MR, Murthy K, Daniel BJ, Wang RF, Thibodeaux SR, Church KM, Hurez V, Kious MJ, Zhang B, Alagbala A, Xia X, Curiel TJ (2013) TgMAPK1 is a Toxoplasma gondii MAP kinase that hijacks host MKK3 signals to regulate virulence and interferon-gamma-mediated nitric oxide production. Exp Parasitol 134:389–399PubMedCentral CrossRef PubMed
  Brumlik MJ, Pandeswara S, Ludwig SM, Murthy K, Curiel TJ (2011) Parasite mitogen-activated protein kinases as drug discovery targets to treat human protozoan pathogens. J Signal Transduct 2011:971968PubMedCentral CrossRef PubMed
  Brumlik MJ, Wei S, Finstad K, Nesbit J, Hyman LE, Lacey M, Burow ME, Curiel TJ (2004) Identification of a novel mitogen-activated protein kinase in Toxoplasma gondii. Int J Parasitol 34:1245–1254CrossRef PubMed
  Cenci-Goga BT, Rossitto PV, Sechi P, McCrindle CM, Cullor JS (2011) Toxoplasma in animals, food, and humans: an old parasite of new concern. Foodborne Pathog Dis 8:751–762CrossRef PubMed
  Contini C, Seraceni S, Cultrera R, Incorvaia C, Sebastiani A, Picot S (2005) Evaluation of a Real-time PCR-based assay using the lightcycler system for detection of Toxoplasma gondii bradyzoite genes in blood specimens from patients with toxoplasmic retinochoroiditis. Int J Parasitol 35:275–383CrossRef PubMed
  Coulthard LR, White DE, Jones DL, McDermott MF, Burchill SA (2009) p38(MAPK): stress responses from molecular mechanisms to therapeutics. Trends Mol Med 15:369–379PubMedCentral CrossRef PubMed
  Cuadrado A, Nebreda AR (2010) Mechanisms and functions of p38 MAPK signalling. Biochem J 429:403–417CrossRef PubMed
  Di Cristina M, Marocco D, Galizi R, Proietti C, Spaccapelo R, Crisanti A (2008) Temporal and spatial distribution of Toxoplasma gondii differentiation into bradyzoites and tissue cyst formation in vivo. Infect Immun 76:3491–3501PubMedCentral CrossRef PubMed
  Donald RG, Roos DS (1993) Stable molecular transformation of Toxoplasma gondii: a selectable dihydrofolate reductase-thymidylate synthase marker based on drug-resistance mutations in malaria. Proc Natl Acad Sci U S A 90:11703–11707PubMedCentral CrossRef PubMed
  Dubey JP (1998) Advances in the life cycle of Toxoplasma gondii. Int J Parasitol 28:1019–1024CrossRef PubMed
  Dubey JP (2009) History of the discovery of the life cycle of Toxoplasma gondii. Int J Parasitol 39:877–882CrossRef PubMed
  Dzierszinski F, Nishi M, Ouko L, Roos DS (2004) Dynamics of Toxoplasma gondii differentiation. Eukaryot Cell 3:992–1003PubMedCentral CrossRef PubMed
  Eaton MS, Weiss LM, Kim K (2006) Cyclic nucleotide kinases and tachyzoite
  adyzoite transition in Toxoplasma gondii. Int J Parasitol 36:107–114PubMedCentral CrossRef PubMed
  Ellis JG, Davila M, Chakrabarti R (2003) Potential involvement of extracellular signal-regulated kinase 1 and 2 in encystation of a primitive eukaryote Giardia lamblia. Stage-specific activation and intracellular localization. J Biol Chem 278:1936–1945CrossRef PubMed
  Fox BA, Belperron AA, Bzik DJ (1999) Stable transformation of Toxoplasma gondii based on a pyrimethamine resistant trifunctional dihydrofolate reductase-cytosine deaminase-thymidylate synthase gene that confers sensitivity to 5-fluorocytosine. Mol Biochem Parasitol 98:93–103CrossRef PubMed
  Hickman MJ, Spatt D, Winston F (2011) The Hog1 mitogen-activated protein kinase mediates a hypoxic response in Saccharomyces cerevisiae. Genetics 188:325–338PubMedCentral CrossRef PubMed
  Holpert M, Gross U, Bohne W (2006) Disruption of the bradyzoite-specific P-type (H+)-ATPase PMA1 in Toxoplasma gondii leads to decreased bradyzoite differentiation after stress stimuli but does not interfere with mature tissue cyst formation. Mol Biochem Parasitol 146:129–133CrossRef PubMed
  Huang H, Ma YF, Bao Y, Lee H, Lisanti MP, Tanowitz HB, Weiss LM (2011) Molecular cloning and characterization of mitogen-activated protein kinase 2 in Toxoplasma gondii. Cell Cycle 10:3519–3526PubMedCentral CrossRef PubMed
  Huynh MH, Rabenau KE, Harper JM, Beatty WL, Sibley LD, Carruthers VB (2003) Rapid invasion of host cells by Toxoplasma requires secretion of the MIC2-M2AP adhesive protein complex. EMBO J 22:2082–2090PubMedCentral CrossRef PubMed
  Johnson GL, Lapadat R (2002) Mitogen-activated protein kinase pathways mediated by ERK, JNK, and p38 protein kinases. Science 298:1911–1912CrossRef PubMed
  Keshet Y, Seger R (2010) The MAP kinase signaling cascades: a system of hundreds of components regulates a diverse array of physiological functions. Methods Mol Biol 661:3–38CrossRef PubMed
  Kibe MK, Coppin A, Dendouga N, Oria G, Meurice E, Mortuaire M, Madec E, Tomavo S (2005) Transcriptional regulation of two stage-specifically expressed genes in the protozoan parasite Toxoplasma gondii. Nucleic Acids Res 33:1722–1736PubMedCentral CrossRef PubMed
  Kim K, Soldati D, Boothroyd JC (1993) Gene replacement in Toxoplasma gondii with chloramphenicol acetyltransferase as selectable marker. Science 262:911–914CrossRef PubMed
  Kuhn D, Wiese M (2005) LmxPK4, a mitogen-activated protein kinase kinase homologue of Leishmania mexicana with a potential role in parasite differentiation. Mol Microbiol 56:1169–1182CrossRef PubMed
  Kyosseva SV (2004) Mitogen-activated protein kinase signaling. Int Rev Neurobiol 59:201–220CrossRef PubMed
  Lacey MR, Brumlik MJ, Yenni RE, Burow ME, Curiel TJ (2007) Toxoplasma gondii expresses two mitogen-activated protein kinase genes that represent distinct protozoan subfamilies. J Mol Evol 64:4–14CrossRef PubMed
  Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) Method. Methods 25:402–408CrossRef PubMed
  Low H, Lye YM, Sim TS (2007) Pfnek3 functions as an atypical MAPKK in Plasmodium falciparum. Biochem Biophys Res Commun 361:439–444CrossRef PubMed
  Lye YM, Chan M, Sim TS (2006) Pfnek3: an atypical activator of a MAP kinase in Plasmodium falciparum. FEBS Lett 580:6083–6092CrossRef PubMed
  Lyons RE, McLeod R, Roberts CW (2002) Toxoplasma gondii tachyzoite
  adyzoite interconversion. Trends Parasitol 18:198–201CrossRef PubMed
  Montoya JG, Liesenfeld O (2004) Toxoplasmosis. Lancet 363:1965–1976CrossRef PubMed
  Morales MA, Pescher P, Spath GF (2010) Leishmania major MPK7 protein kinase activity inhibits intracellular growth of the pathogenic amastigote stage. Eukaryot Cell 9:22–30PubMedCentral CrossRef PubMed
  Patil V, Lescault PJ, Lirussi D, Thompson AB, Matrajt M (2012) Disruption of the expression of a non-coding RNA significantly impairs cellular differentiation in Toxoplasma gondii. Int J Mol Sci 14:611–624PubMedCentral CrossRef PubMed
  Pszenny V, Davis PH, Zhou XW, Hunter CA, Carruthers VB, Roos DS (2011) Targeted disruption of Toxoplasma gondii serine protease inhibitor 1 increases bradyzoite cyst formation in vitro and parasite tissue burden in mice. Infect Immun 80:1156–1165CrossRef PubMed
  Que X, Engel JC, Ferguson D, Wunderlich A, Tomavo S, Reed SL (2007) Cathepsin Cs are key for the intracellular survival of the protozoan parasite, Toxoplasma gondii. J Biol Chem 282:4994–5003CrossRef PubMed
  Rooney PJ, Neal LM, Knoll LJ (2011) Involvement of a Toxoplasma gondii chromatin remodeling complex ortholog in developmental regulation. PLoS One 6, e19570PubMedCentral CrossRef PubMed
  Roisin MP, Robert-Gangneux F, Creuzet C, Dupouy-Camet J (2000) Biochemical characterization of mitogen-activated protein (MAP) kinase activity in Toxoplasma gondii. Parasitol Res 86:588–598CrossRef PubMed
  Saeij JP, Arrizabalaga G, Boothroyd JC (2008) A cluster of four surface antigen genes specifically expressed in bradyzoites, SAG2CDXY, plays an important role in Toxoplasma gondii persistence. Infect Immun 76:2402–2410PubMedCentral CrossRef PubMed
  Selseleh M, Modarressi MH, Mohebali M, Shojaee S, Eshragian MR, Selseleh M, Azizi E, Keshavarz H (2012) Real-time RT-PCR on SAG1 and BAG1 gene expression during stage conversion in immunosuppressed mice infected with Toxoplasma gondii Tehran strain. Korean J Parasitol 50:199–205PubMedCentral CrossRef PubMed
  Skariah S, McIntyre MK, Mordue DG (2010) Toxoplasma gondii: determinants of tachyzoite to bradyzoite conversion. Parasitol Res 107:253–260PubMedCentral CrossRef PubMed
  Soete M, Camus D, Dubremetz JF (1994) Experimental induction of bradyzoite-specific antigen expression and cyst formation by the RH strain of Toxoplasma gondii in vitro. Exp Parasitol 78:361–370CrossRef PubMed
  Starnes GL, Coincon M, Sygusch J, Sibley LD (2009) Aldolase is essential for energy production and bridging adhesin-actin cytoskeletal interactions during parasite invasion of host cells. Cell Host Microbe 5:353–364PubMedCentral CrossRef PubMed
  Tenter AM, Heckeroth AR, Weiss LM (2000) Toxoplasma gondii: from animals to humans. Int J Parasitol 30:1217–1258PubMedCentral CrossRef PubMed
  Unno A, Suzuki K, Batanova T, Cha SY, Jang HK, Kitoh K, Takashima Y (2009) Visualization of Toxoplasma gondii stage conversion by expression of stage-specific dual fluorescent proteins. Parasitology 136:579–588CrossRef PubMed
  Vanchinathan P, Brewer JL, Harb OS, Boothroyd JC, Singh U (2005) Disruption of a locus encoding a nucleolar zinc finger protein decreases tachyzoite-to
  adyzoite differentiation in Toxoplasma gondii. Infect Immun 73:6680–6688PubMedCentral CrossRef PubMed
  Walker R, Gissot M, Croken MM, Huot L, Hot D, Kim K, Tomavo S (2013) The Toxoplasma nuclear factor TgAP2XI-4 controls bradyzoite gene expression and cyst formation. Mol Microbiol 87:641–655PubMedCentral CrossRef PubMed
  Wei F, Wang W, Liu Q (2013) Protein kinases of Toxoplasma gondii: functions and drug targets. Parasitol Res 112:2121–129CrossRef PubMed
  Wei S, Marches F, Daniel B, Sonda S, Heidenreich K, Curiel T (2002) Pyridinylimidazole p38 mitogen-activated protein kinase inhibitors block intracellular Toxoplasma gondii replication. Int J Parasitol 32:969–977CrossRef PubMed
  Weilhammer DR, Iavarone AT, Villegas EN, Brooks GA, Sinai AP, Sha WC (2012) Host metabolism regulates growth and differentiation of Toxoplasma gondii. Int J Parasitol 42:947–959PubMedCentral CrossRef PubMed
  Weiss LM, Kim K (2000) The development and biology of bradyzoites of Toxoplasma gondii. Front Biosci 5:391–405CrossRef
  Widmann C, Gibson S, Jarpe MB, Johnson GL (1999) Mitogen-activated protein kinase: conservation of a three-kinase module from yeast to human. Physiol Rev 79:143–180PubMed
  
• 作者单位：Lili Cao (1) (2)
  Zedong Wang (1)
  Shuchao Wang (1)
  Jiping Li (1)
  Xinglong Wang (1)
  Feng Wei (3)
  Quan Liu (1)
  
  1. Military Veterinary Institute, Academy of Military Medical Sciences, Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Changchun, 130122, Jilin Province, People’s Republic of China
  2. Academy of Animal Husbandry and Veterinary Medicine, Changchun, 130062, Jilin Province, People’s Republic of China
  3. College of Life Science, Jilin Agricultural University, Changchun, 130118, Jilin Province, People’s Republic of China
  
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Biomedicine
  Medical Microbiology
  Microbiology
  Immunology
  
• 出版者：Springer Berlin / Heidelberg
• ISSN：1432-1955

文摘

Mitogen-activated protein kinases (MAPKs) regulate key signaling events in a variety of eukaryotic cells. Toxoplasma gondii, the causative agents of toxoplasmosis, possesses a p38α MAPK homologue, MAPK1, which is an important manipulator of host immunity and virulence in mice. In this work, we showed an increased transcript level of MAPK1 in T. gondii during bradyzoite differentiation induced by alkaline treatment and heat shock in vitro, suggesting that MAPK1 may be associated with bradyzoite differentiation. The biological roles of MAPK1 of T. gondii were investigated by construction of a MAPK1 deletion mutant (Δmapk1) and a complementation mutant with restored MAPK1 expression using a type I strain. Knockout of MAPK1 resulted in markedly defective bradyzoite differentiation, host-cell attachment and parasite replication in vitro, and the inability to cause lethal infection in a murine model of acute toxoplasmosis, with lower parasite burden in infected tissues, showing that MAPK1 is associated with the acute virulence of parasite in mice. Complementation of MAPK1-deficient parasites restored bradyzoite development, attachment, replication, and virulence. Our findings demonstrate that MAPK1 is involved in asexual development and growth of T. gondii. Keywords Toxoplasma gondii Mitogen-activated protein kinase Asexual development Growth