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Understanding the Cellular Functions Polyamines Play in Proliferation, Replication, and Survival of Leishmania donovani
Author(s) -
Perdeh Jasmine,
Love Quintin,
Leizorek Yvette,
Berioso Brandon,
Le Linh,
Roberts Sigrid
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.06858
Subject(s) - putrescine , spermidine , ornithine decarboxylase , polyamine , biology , leishmania donovani , cell growth , leishmania , ornithine decarboxylase antizyme , microbiology and biotechnology , biochemistry , immunology , enzyme , leishmaniasis , visceral leishmaniasis , parasite hosting , world wide web , computer science
Leishmaniasis, a neglected tropical disease, affects an estimated billion people worldwide. A better understanding of parasite biology is vital for the development of much needed new therapeutic strategies. Our research addresses this critical need by focusing on the role of polyamines for growth and survival of Leishmania parasites. The main polyamine biosynthetic enzymes in Leishmania are ornithine decarboxylase (ODC) and spermidine synthase (SPDSYN), which sequentially convert ornithine to the polyamines, putrescine and spermidine. With generated gene deletion mutants, Δodc and Δspdsyn , we have demonstrated in vitro that the metabolite putrescine is essential beyond its function as the precursor for spermidine formation. Additionally, we observed that putrescine‐depleted Δodc parasites immediately ceased proliferation and died within two weeks. In contrast, putrescine‐rich Δspdsyn mutants showed an intermediate growth phenotype and entered a quiescent‐like state with cell death occurring after six weeks. Furthermore, putrescine‐depleted cells were unable to synthesize DNA and stopped replicating. We also observed two hallmarks of programmed cell death in the putrescine‐depleted cells: cell‐rounding and phosphatidylserine exposure. To reduce the variability associated with working with two cell lines and to further understand the functions polyamines play, we are in the process of generating a double gene deletion mutant, ΔodcΔspdsyn . Support or Funding Information Pacific University School of Pharmacy Research Incentive Grant