TCP1 γ subunit is indispensable for growth and infectivity of Leishmania donovani.

TCP1γ subunit is indispensable for growth and infectivity of Leishmania donovani. Antimicrob Agents Chemother. 2020 May 26;: Authors: Yadav S, Kuldeep J, Siddiqi MI, Goyal N Abstract T-complex protein-1 (TCP1) is a ubiquitous group II chaperonin and is known to fold various proteins like actin and tubulin. In Leishmania donovani, γ subunit of TCP1 (LdTCP1γ) has been cloned and characterized. It forms high molecular weight, homo-oligomeric complex that performs ATP dependent protein folding. In the present study, we evaluated the essentiality of LdTCP1γ gene. Gene replacement studies indicate that LdTCP1γ is essential for parasite survival. The LdTCP1γ single-allele replacement mutants exhibited slowed growth and decreased infectivity in mouse macrophages compared to the wild-type parasites. Modulation of LdTCP1γ expression in promastigotes, also modulate cell cycle progression. Suramin, an anti-trypanosomal drug, not only inhibited the luciferase refolding activity of recombinant LdTCP1γ homo-oligomeric complex but also exhibited potential antileishmanial efficacy both in vitro and in vivo. The interaction of suramin and LdTCP1γ was further validated by isothermal titration calorimetry. The study suggests LdTCP1γ as potential drug target and also provides a framework for the development of a new class of drugs. PMID: 32457112 [PubMed - as supplied by publisher]
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research