My research focuses on the importance in vivo of the oxygen (O2) sensors on the parasite Toxoplasma gondii adaptability to the different levels of O2 in the tissues, during its complex life cycle in the infected host.
Toxoplasmosis caused by Toxoplasma gondii an obligate intracellular parasite, is an important opportunistic infection in AIDS patients and immunocompromised individuals. Human infection typically occurs through the ingestion of contaminated food. After breaching the intestinal epithelial barrier, the parasite spreads to a large variety of other organs such as the brain, eyes and placenta. During its journeys throughout the tissues in the infected host, Toxoplasma is exposed to diverse O2 tensions and must adapt to changes in O2 availability for its survival and virulence.
Previous work in the Blader lab revealed that Toxoplasma reacts to changes in O2 availability using its own O2 sensing machinery (prolyl 4-hydroxylases; PHDs) and by activating HIF-1α, the host cell transcription factor that mediates cellular responses to low O2. The loss by genetic disruption of the parasite PHDs or the host cell transcription factor HIF-1α, reduces parasite growth in vitro in an O2-dependent manner. Moreover, HIF-1α regulates the function of many cells like macrophages and monocytes, which are required for host resistance to Toxoplasma infection and may impact its virulence.
The importance in vivo of the O2 sensors during Toxoplasma life cycle in the infected host has not been investigated yet. It is the goal of my research to understand the impact of the O2 sensors on Toxoplasma virulence to generate a successful infection in which parasites can disseminate from the gut and form tissue cysts. We use a mouse model infected with Toxoplasma PHDs mutant tissue cysts and a mouse strain in which HIF-1α is deleted in myeloid cells, which included macrophages and monocytes. Understand the role of the O2 sensors and identify the pathways involved could define new potential targets to anti-Toxoplasma drugs.
Charlotte Cordonnier, PhD
955 Main Street, Suite 5260
Phone: (716) 645-6790