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Opposing transcriptional forces underlie chronic disease caused by Toxoplasma gondii
Author(s) -
White Michael,
Hong DongPyo,
Worth Danielle,
Huang Sherri,
Radke Josh,
Sullivan William,
Wilson Emma
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.270.4
Subject(s) - toxoplasma gondii , biology , cyst , disease , pathogenesis , transcriptome , chronic infection , immunology , gene , microbiology and biotechnology , genetics , pathology , gene expression , medicine , immune system , antibody
Toxoplasma gondii infections continue to be a public health hazard for millions of individuals that contact this pathogen annually. More than 50 million individuals in the US are chronically infected with Toxoplasma gondii and thousands of healthy individuals develop eye disease due to this infection that can lead to permanent vision loss. The Centers for Disease Control and Prevention considers Toxoplasma one of the five most important neglected parasitic infections. Toxoplasma infections are life‐long due to the development of the bradyzoite‐tissue cyst. No current drug successfully treats or prevents the tissue cyst and this therapy failure leaves individuals who become infected vulnerable to disease relapse throughout their lifetimes. Despite the important clinical consequences of this developmental pathway, the molecular basis of the switch mechanisms that control formation of the tissue cyst is still poorly understood. Significant changes in gene expression are required to form the bradyzoite‐tissue cyst and ApiAP2 transcription factors are an important mechanism regulating this developmental transcriptome. ApiAP2 factors are a large family of proteins (67) in Toxoplasma that are distantly related to AP2 transcription factors of plants and not found in the human host. We will discuss our recent studies that have uncovered a complex ApiAP2 transcriptional network of repressors and activators competing at the interface of tachyzoite replication and early switching to regulate tissue cyst formation. We believe Toxoplasma may have evolved this complex transcriptional network to balance the competing demands of expanding the acute stage (tachyzoite) responsible for pathogenesis with the production of the dormant bradyzoite‐tissue cyst that is invisible to the immune system and required for transmission. Support or Funding Information National Institutes of Health, R01AI122760, R01AI09843, R56AI124682