Abstract
ABSTRACTToxoplasma gondii is one of the most common parasitic infections of humans worldwide. Once exposed, humans remain infected with T. gondii for life, and there are no therapeutics capable of eliminating a chronic infection. In the search for novel drug targets, T. gondii is known to contain several unique secretory organelles, one of which is called the rhoptries. Rhoptry organelles contain and secrete numerous proteins with kinase domains, but the roles of most of these kinases during infection remain unknown. In a recent mBio article, B. A. Fox et al. [mBio 7(3):e00193-16, 2016, http://dx.doi.org/10.1128/mBio.00193-16] performed a tour de force deletion analysis of 31 rhoptry kinases and examined their roles in the development of chronic infection. While rhoptry kinase deletion strains that displayed an acute infection defect also showed a reduction in chronic infection cyst burden, two rhoptry kinase deletion strains had decreased cyst burden without any change in acute virulence. These results indicate the necessity of the rhoptry kinases for the establishment and perhaps maintenance of chronic infection. They also highlight the potential of these kinases as drug targets to clear chronic infection or as candidates to generate a nonpersisting vaccine.
Highlights
Toxoplasma gondii is one of the most common parasitic infections of humans worldwide
Toxoplasmic encephalitis most often occurs in immunocompromised patients when the chronic cyst stage reactivates as cellular immune surveillance is lost [3]; T. gondii was notorious during the AIDS pandemic as a major cause of encephalitis
Investigating the roles of these rhoptry kinases during different life cycle stages opens a window to determine novel drug targets that are active against alternative stages, such as bradyzoite cysts
Summary
Toxoplasma gondii is one of the most common parasitic infections of humans worldwide. Investigating the roles of these rhoptry kinases during different life cycle stages opens a window to determine novel drug targets that are active against alternative stages, such as bradyzoite cysts. They deleted 32 identified members of the rhoptry kinase gene family in a type II strain of T. gondii.
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