Leishmania donovani, while invading macrophages, encounters striking shift in temperature and pH (from 22°C and pH 7.2 to 37°C and pH 5.5), which act as the key environmental trigger for differentiation, and increases cAMP level and cAMP-mediated responses. For comprehensive understanding of cAMP signaling, we studied the
enzymes related to cAMP metabolism. A stage-specific and developmentally regulated
isoform of receptor
adenylate cyclase (LdRACA) showed to regulate differentiation-coupled induction of cAMP. The soluble acidocalcisomal
pyrophosphatase, Ldvsp1, was the major
isoform regulating cAMP level in association with LdRACA. A differentially expressed soluble cytosolic
cAMP phosphodiesterase (LdPDEA) might be related to
infection establishment by shifting
trypanothione pool utilization bias toward
antioxidant defense. We identified and cloned a functional cAMP-binding effector molecule from L. donovani (a regulatory subunit of
cAMP-dependent protein kinase, LdPKAR) that may modulate metacyclogenesis through induction of autophagy. This study reveals the significance of cAMP signaling in parasite survival and infectivity.