Identification and characterization of yeast SNF1 kinase homologs in Leishmania major

BackgroundSucrose Non Fermenting1 (SNF1) constitutes a family of protein kinases conserved in eukaryotes, plants, and fungi. SNF1 has been known to play a crucial role in stress adaptation and metabolism, enabling organisms to respond to changing environmental conditions. Initially identified in yea...

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Main Authors: Gaurav Shoeran, Namrata Anand, Upninder Kaur, Kapil Goyal, Rakesh Sehgal
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-03-01
Series:Frontiers in Molecular Biosciences
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Online Access:https://www.frontiersin.org/articles/10.3389/fmolb.2025.1567703/full
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author Gaurav Shoeran
Namrata Anand
Upninder Kaur
Kapil Goyal
Rakesh Sehgal
author_facet Gaurav Shoeran
Namrata Anand
Upninder Kaur
Kapil Goyal
Rakesh Sehgal
author_sort Gaurav Shoeran
collection DOAJ
description BackgroundSucrose Non Fermenting1 (SNF1) constitutes a family of protein kinases conserved in eukaryotes, plants, and fungi. SNF1 has been known to play a crucial role in stress adaptation and metabolism, enabling organisms to respond to changing environmental conditions. Initially identified in yeast, SNF1 is essential for shifting from the primary carbon source, glucose, to secondary carbon sources like sucrose. Homologs of this protein family were identified in Leishmania major, a protozoan parasite and we aimed to determine their role in this parasite.MethodsIn the present study, we identified the putative homologs of SNF1 kinase in L. major and knock out strains were prepared using the CRISPR-Cas9 knock-out strategy. The developed strains were evaluated for their growth, characteristics, protein expression and ultra structural changes in vitro and virulence in a mouse model.ResultsOne of the strain named N2, was found to be completely avirulent and showed limited growth, lack of glycosomes and had a fewer mitochondria with deformed cristae. The N2 strain failed to produce infection in mice when compared to WT mice. Proteome analysis revealed an increase in ribosomal proteins in the N2 strain, highlighting the role of ribosomes in stress adaptation.ConclusionThe essentiality of this gene for developing infections in mice underscores its potential in the development of future antileishmanial therapies and live attenuated strains.
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spelling doaj-art-2bb843e2bee3465d9a8681b0a65bcfd72025-08-20T01:48:38ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2025-03-011210.3389/fmolb.2025.15677031567703Identification and characterization of yeast SNF1 kinase homologs in Leishmania majorGaurav Shoeran0Namrata Anand1Upninder Kaur2Kapil Goyal3Rakesh Sehgal4Department of Medical Parasitology, Postgraduate Institute of Medical Education and Research, Chandigarh, IndiaDepartment of Medical Parasitology, Postgraduate Institute of Medical Education and Research, Chandigarh, IndiaDepartment of Medical Parasitology, Postgraduate Institute of Medical Education and Research, Chandigarh, IndiaDepartment of Virology, Postgraduate Institute of Medical Education and Research, Chandigarh, IndiaDepartment of Medical Parasitology, Postgraduate Institute of Medical Education and Research, Chandigarh, IndiaBackgroundSucrose Non Fermenting1 (SNF1) constitutes a family of protein kinases conserved in eukaryotes, plants, and fungi. SNF1 has been known to play a crucial role in stress adaptation and metabolism, enabling organisms to respond to changing environmental conditions. Initially identified in yeast, SNF1 is essential for shifting from the primary carbon source, glucose, to secondary carbon sources like sucrose. Homologs of this protein family were identified in Leishmania major, a protozoan parasite and we aimed to determine their role in this parasite.MethodsIn the present study, we identified the putative homologs of SNF1 kinase in L. major and knock out strains were prepared using the CRISPR-Cas9 knock-out strategy. The developed strains were evaluated for their growth, characteristics, protein expression and ultra structural changes in vitro and virulence in a mouse model.ResultsOne of the strain named N2, was found to be completely avirulent and showed limited growth, lack of glycosomes and had a fewer mitochondria with deformed cristae. The N2 strain failed to produce infection in mice when compared to WT mice. Proteome analysis revealed an increase in ribosomal proteins in the N2 strain, highlighting the role of ribosomes in stress adaptation.ConclusionThe essentiality of this gene for developing infections in mice underscores its potential in the development of future antileishmanial therapies and live attenuated strains.https://www.frontiersin.org/articles/10.3389/fmolb.2025.1567703/fullLeishmania majorSNF1CRISPR-Cas9stress adaptationribosomes
spellingShingle Gaurav Shoeran
Namrata Anand
Upninder Kaur
Kapil Goyal
Rakesh Sehgal
Identification and characterization of yeast SNF1 kinase homologs in Leishmania major
Frontiers in Molecular Biosciences
Leishmania major
SNF1
CRISPR-Cas9
stress adaptation
ribosomes
title Identification and characterization of yeast SNF1 kinase homologs in Leishmania major
title_full Identification and characterization of yeast SNF1 kinase homologs in Leishmania major
title_fullStr Identification and characterization of yeast SNF1 kinase homologs in Leishmania major
title_full_unstemmed Identification and characterization of yeast SNF1 kinase homologs in Leishmania major
title_short Identification and characterization of yeast SNF1 kinase homologs in Leishmania major
title_sort identification and characterization of yeast snf1 kinase homologs in leishmania major
topic Leishmania major
SNF1
CRISPR-Cas9
stress adaptation
ribosomes
url https://www.frontiersin.org/articles/10.3389/fmolb.2025.1567703/full
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AT upninderkaur identificationandcharacterizationofyeastsnf1kinasehomologsinleishmaniamajor
AT kapilgoyal identificationandcharacterizationofyeastsnf1kinasehomologsinleishmaniamajor
AT rakeshsehgal identificationandcharacterizationofyeastsnf1kinasehomologsinleishmaniamajor