Open AccessThe host cell transcription factor hypoxia‐inducible factor 1 is required for Toxoplasma gondii growth and survival at physiological oxygen levels
Author(s) -
Spear Wade,
Chan Denise,
Coppens Isabelle,
Johnson Randall S.,
Giaccia Amato,
Blader Ira J.
Publication year - 2006
Publication title -
cellular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.542
H-Index - 138
eISSN - 1462-5822
pISSN - 1462-5814
DOI - 10.1111/j.1462-5822.2005.00628.x
Subject(s) - biology , toxoplasma gondii , transcription factor , hypoxia inducible factors , hypoxia (environmental) , microbiology and biotechnology , cancer research , oxygen , immunology , genetics , gene , antibody , chemistry , organic chemistry
Summary Toxoplasma gondii is an obligate intracellular protozoan pathogen. We previously found that genes mediating cellular responses to hypoxia were upregulated in Toxoplasma ‐infected cells but not in cells infected with another intracellular pathogen, Trypanosoma cruzi . The inducible expression of these genes is controlled by the hypoxia‐inducible factor 1 (HIF1) transcription factor, which is the master regulator of cells exposed to low oxygen. Because this response may be important for parasites to grow at physiological oxygen levels, we tested the hypothesis that HIF1 is important for Toxoplasma growth. Here, we demonstrate that Toxoplasma infection rapidly increased the abundance of the HIF1α subunit and activated HIF1 reporter gene expression. In addition, we found that Toxoplasma growth and survival was severely reduced in HIF1α knockout cells at 3% oxygen. While HIF1α was not required for parasite invasion, we determined that HIF1 was required for parasite cell division and organelle maintenance at 3% oxygen. These data indicate that Toxoplasma activates HIF1 and requires HIF1 for growth and survival at physiologically relevant oxygen levels.