Deletion of Glutamine Synthetase Gene Disrupts the Survivability and Infectivity of Leishmania donovani

Infectivity Propidium iodide
DOI: 10.3389/fcimb.2021.622266 Publication Date: 2021-02-26T07:41:47Z
ABSTRACT
Glutamine synthetase (GS) is one of the most important metabolic enzymes which catalyzes ligation glutamate and ammonia to form glutamine. Previous studies from our lab had revealed significant differences in parasite host GS enzyme warranted us further work on its relevance parasite. To analyze glutamine function Leishmania , we generated overexpressors knockout mutants evaluated their ability grow vitro monocyte differentiated macrophage vivo by infections BALB/c mice. knocked out strain showed growth retardation with delayed cell cycle progression morphological alteration. Null exhibited attenuated infectivity both experiments effect was reverted back when infected complemented parasites. This indicated that alterations phenotype observed were indeed due knockout. also made increasingly sensitive Miltefosine. Detailed investigation mode death upon Miltefosine treatment dual staining Annexin-V conjugated FITC propidium iodide, pointed towards apoptotic or necrotic death. first report confirm essential for survivability donovani can be exploited as a potential drug-target.
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