Identification of Potent Phosphodiesterase Inhibitors that Demonstrate Cyclic Nucleotide-Dependent Functions in Apicomplexan Parasites
Brittany L Howard, Katherine L Harvey, Rebecca J Stewart, Mauro F Azevedo, Brendan S Crabb, Ian G Jennings, Paul R Sanders, David T Manallack, Philip E Thompson, Christopher J Tonkin, Paul R Gilson
ACS CHEMICAL BIOLOGY | AMER CHEMICAL SOC | Published : 2015
Apicomplexan parasites, including Plasmodium falciparum and Toxoplasma gondii, the causative agents of severe malaria and toxoplasmosis, respectively, undergo several critical developmental transitions during their lifecycle. Most important for human pathogenesis is the asexual cycle, in which parasites undergo rounds of host cell invasion, replication, and egress (exit), destroying host cell tissue in the process. Previous work has identified important roles for Protein Kinase G (PKG) and Protein Kinase A (PKA) in parasite egress and invasion, yet little is understood about the regulation of cyclic nucleotides, cGMP and cAMP, that activate these enzymes. To address this, we have focused upo..View full abstract
Awarded by Australian Future Fellowship
Awarded by NHMRC
B.L.H., K.L.H., and R.J.S. are recipients of Australian Postgraduate Awards, and C.J.T is recipient of an Australian Future Fellowship (FT1200100164). This work was supported by NHMRC Project grants 1025598 and 603720 as well as the Victorian State Government Operational Infrastructure Support Program and NHMRC IRIISS. We are grateful to the Australian Red Cross for the supply of red blood. cells. We also thank K. Rogers for help with microscopy and T. Luc for technical assistance.