Characterization of an Entamoeba histolytica high-mobility-group box protein induced during intestinal infection

被引:20
作者
Abhyankar, Mayuresh M. [1 ]
Hochreiter, Amelia E. [1 ,2 ]
Hershey, Jessica [2 ]
Evans, Clive [4 ]
Zhang, Yan [4 ]
Crasta, Oswald [4 ]
Sobral, Bruno W. S. [4 ]
Mann, Barbara J. [1 ,2 ]
Petri, William A., Jr. [1 ,2 ,3 ]
Gilchrist, Carol A. [1 ]
机构
[1] Univ Virginia, Dept Med, Charlottesville, VA USA
[2] Univ Virginia, Dept Microbiol, Charlottesville, VA 22908 USA
[3] Univ Virginia, Dept Pathol, Charlottesville, VA 22903 USA
[4] Virginia Tech, Virginia Bioinformat Inst, Blacksburg, VA USA
关键词
D O I
10.1128/EC.00123-08
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
The unicellular eukaryote Entamoeba histolytica is a human parasite that causes amebic dysentery and liver abscess. A genome-wide analysis of gene expression modulated by intestinal colonization and invasion identified an upregulated transcript that encoded a putative high-mobility-group box (HMGB) protein, EhHMGB1. We tested if EhHMGB1 encoded a functional HMGB protein and determined its role in control of parasite gene expression. Recombinant EhHMGB1 was able to bend DNA in vitro, a characteristic of HMGB proteins. Core conserved residues required for DNA bending activity in other HMGB proteins were demonstrated by mutational analysis to be essential for EhHMGB1 activity. EhHMGB1 was also able to enhance the binding of human p53 to its cognate DNA sequence in vitro, which is expected for an HMGB1 protein. Confocal microscopy, using antibodies against the recombinant protein, confirmed its nuclear localization. Overexpression of EhHMGB1 in HM1:IMSS trophozoites led to modulation of 33 transcripts involved in a variety of cellular functions. Of these, 20 were also modulated at either day 1 or day 29 in the mouse model of intestinal amebiasis. Notably, four transcripts with known roles in virulence, including two encoding Gal/GalNAc lectin light chains, were modulated in response to EhHMGB1 overexpression. We concluded that EhHMGB1 was a bona fide HMGB protein with the capacity to recapitulate part of the modulation of parasite gene expression seen during adaptation to the host intestine.
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页码:1565 / 1572
页数:8
相关论文
共 69 条
[1]   HMGB1 interacts differentially with members of the Rel family of transcription factors [J].
Agresti, A ;
Lupo, R ;
Bianchi, ME ;
Müller, S .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2003, 302 (02) :421-426
[2]   HMGB proteins and gene expression [J].
Agresti, A ;
Bianchi, ME .
CURRENT OPINION IN GENETICS & DEVELOPMENT, 2003, 13 (02) :170-178
[3]   Genes induced by a high-oxygen environment in Entamoeba histolytica [J].
Akbar, MA ;
Chatterjee, NS ;
Sen, P ;
Debnath, A ;
Pal, A ;
Bera, T ;
Das, P .
MOLECULAR AND BIOCHEMICAL PARASITOLOGY, 2004, 133 (02) :187-196
[4]   Antisense inhibition of expression of the light subunit (35 kDa) of the Gal/GalNac lectin complex inhibits Entamoeba histolytica virulence [J].
Ankri, S ;
Padilla-Vaca, F ;
Stolarsky, T ;
Koole, L ;
Katz, U ;
Mirelman, D .
MOLECULAR MICROBIOLOGY, 1999, 33 (02) :327-337
[5]   Resistance to intestinal Entamoeba histolytica infection is conferred by innate immunity and Gr-1+ cells [J].
Asgharpour, A ;
Gilchrist, C ;
Baba, D ;
Hamano, S ;
Houpt, E .
INFECTION AND IMMUNITY, 2005, 73 (08) :4522-4529
[6]   Transcriptional upregulation of genes related to virulence activation in Entamoeba histolytica [J].
Balderas-Renteria, Isaias ;
Garcia-Lazaro, J. Francisco ;
Carranza-Rosales, Pilar ;
Morales-Ramos, Lilia H. ;
Galan-Wong, Luis J. ;
Munoz-Espinosa, Linda E. .
ARCHIVES OF MEDICAL RESEARCH, 2007, 38 (04) :372-379
[7]   Cloning the genes and DNA binding properties of High Mobility Group B1 (HMGB1) proteins from the human blood flukes Schistosoma mansoni and Schistosoma japonicum [J].
Bastos de Oliveira, Francisco Meirelles ;
de Abreu da Silva, Isabel Caetano ;
Rumjanek, Franklin David ;
Dias-Neto, Emmanuel ;
Moreira Guimaraes, Pedro Edson ;
Verjovski-Almeida, Sergio ;
Stros, Michal ;
Fantappie, Marcelo Rosado .
GENE, 2006, 377 :33-45
[8]   HOMOLOGY MODEL-BUILDING OF THE HMG-1 BOX STRUCTURAL DOMAIN [J].
BAXEVANIS, AD ;
BRYANT, SH ;
LANDSMAN, D .
NUCLEIC ACIDS RESEARCH, 1995, 23 (06) :1019-1029
[9]   Identification and gene expression analysis of a large family of transmembrane kinases related to the Gal/GalNAc lectin in Entamoeba histolytica [J].
Beck, DL ;
Boettner, DR ;
Dragulev, B ;
Ready, K ;
Nozaki, T ;
Petri, WA .
EUKARYOTIC CELL, 2005, 4 (04) :722-732
[10]   CONTROLLING THE FALSE DISCOVERY RATE - A PRACTICAL AND POWERFUL APPROACH TO MULTIPLE TESTING [J].
BENJAMINI, Y ;
HOCHBERG, Y .
JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES B-STATISTICAL METHODOLOGY, 1995, 57 (01) :289-300