Role of cAMP Signaling in the Survival and Infectivity of the Protozoan Parasite, Leishmania donovani

Figure 2

Model for comprehensive cAMP signaling in Leishmania parasites. Receptor adenylate cyclase A (LdRACA) and receptor adenylate cyclase B (LdRACB) are G-protein independent membranae bound adenylate cyclases (AC). LdRACA primarily converts ATP to cAMP along with the formation of PPi. This PPi pool provides an inhibition to AC towards the formation of cAMP. During stress, the PPi pool is hydrolyzed by vacuolar acidocalcisomal soluble pyrophosphatase (LdVSP1) which is released by membrane disintegration of acidocalcisomes releasing the inhibition on LdRACA to produce more cAMP. The increased level of cAMP stalls the cell cycle of the parasite at G1 stage and also elevates the expression of antioxidant genes like peroxidoxin, superoxide dismutase and tryparedoxin peroxidase. cAMP also downregulates a stage specific cytosolic PDE, LdPDEA leading to peroxide degradation due to trypanothione (TSH) pool utilization bias towards peroxide degradation instead of DNA synthesis by ribonucleotide reductase which helps in the survival of the parasite in macrophages. Moreover, LdPKAR might have a role in the infective metacyclic stage of the parasite as it induces the formation of autophagosome and process of autophagy initiating metacyclogenesis.