An integrative in silico and in vitro study identifies Leishmania donovani MAP kinase12 as a probable virulence factor.

Abstract

Visceral leishmaniasis (VL), a potentially fatal vector-borne disease caused by the intracellular protozoan parasite Leishmania donovani, remains a major health problem due to restricted repertoire of drugs, deleterious side effects, high cost and increasing drug resistance. Therefore, identifying newer drug targets and developing efficacious affordable treatments with minimal or no side effects are pressing needs. Being regulators of diverse cellular processes, Mitogen-Activated Protein Kinases (MAPKs) are potential drug targets. Herein, we report L.donovani MAPK12 (LdMAPK12) as a probable virulence factor implying it as a plausible target. LdMAPK12 sequence is distinct from human MAPKs and is highly conserved in different Leishmania species. LdMAPK12 is expressed in both promastigotes and amastigotes. In comparison with the avirulent and procyclic promastigotes, the virulent and metacyclic promastigotes have higher expression of LdMAPK12. Pro-inflammatory cytokines reduced, whereas anti-inflammatory cytokines increased LdMAPK12 expression in macrophages. These data suggest a probable novel role of LdMAPK12 in parasite virulence and identifies it as a plausible drug target.