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

Abstract EN

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.