Characterization of a novel amastin-like surface protein (ALSP) of<i>Leishmania donovani</i>, a probable lipase

Biswas, Bapi; Laha, Bhakti; Ghosh, Monidipa

doi:10.1101/2020.07.23.218107

Cited by 5 publications

(3 citation statements)

References 62 publications

(100 reference statements)

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“…GP63 is a plasma membrane localized metalloprotease in both promastigotes and amastigotes [63], with secondary localizations within the reticulum endoplasmic, flagellar pocket, and with a secreted form known too [64,65]. In promastigotes, GP63 increases during the transition to the stationary phase, and is abundant in the infective non-proliferative metacyclics [66,67]. Upon transmission to a mammalian host, GP63 plays a key role in the evasion and inactivation of the host's innate immune system [68].…”

Section: Discussionmentioning

confidence: 99%

Transcriptional Shift and Metabolic Adaptations during Leishmania Quiescence Using Stationary Phase and Drug Pressure as Models

et al. 2022

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Microorganisms can adopt a quiescent physiological condition which acts as a survival strategy under unfavorable conditions. Quiescent cells are characterized by slow or non-proliferation and a deep downregulation of processes related to biosynthesis. Although quiescence has been described mostly in bacteria, this survival skill is widespread, including in eukaryotic microorganisms. In Leishmania, a digenetic parasitic protozoan that causes a major infectious disease, quiescence has been demonstrated, but the molecular and metabolic features enabling its maintenance are unknown. Here, we quantified the transcriptome and metabolome of Leishmania promastigotes and amastigotes where quiescence was induced in vitro either, through drug pressure or by stationary phase. Quiescent cells have a global and coordinated reduction in overall transcription, with levels dropping to as low as 0.4% of those in proliferating cells. However, a subset of transcripts did not follow this trend and were relatively upregulated in quiescent populations, including those encoding membrane components, such as amastins and GP63, or processes like autophagy. The metabolome followed a similar trend of overall downregulation albeit to a lesser magnitude than the transcriptome. It is noteworthy that among the commonly upregulated metabolites were those involved in carbon sources as an alternative to glucose. This first integrated two omics layers afford novel insight into cell regulation and show commonly modulated features across stimuli and stages.

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Section: Discussionmentioning

confidence: 99%

Transcriptional Shift and Metabolic Adaptations during Leishmania Quiescence Using Stationary Phase and Drug Pressure as Models

et al. 2022

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“…Amastin surface like-proteins (ALSP), low molecular weight proteins analogous to amastins, were also upregulated during quiescence. In L. donovani amastigotes ALSPs have been proposed to function as triglyceride lipases generating glycerol and fatty acids that can be transported into the parasite to support energy generation and the synthesis of specialised lipids [62]. Intriguingly, despite their name ALSP have a cytoplasmatic localization near to the flagellar pocket and, as is true for other lipases in Leishmania, they can be secreted.…”

Section: Discussionmentioning

confidence: 99%

Transcriptional shift and metabolic adaptations during Leishmania quiescence using stationary-phase and drug pressure as models

Jara

Barrett

Maes

et al. 2021

Preprint

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Microorganisms can adopt a quiescent physiological condition which acts as a survival strategy under unfavourable conditions. Quiescent cells are characterized by slow or non-proliferation and deep down-regulation of processes related to biosynthesis. Although quiescence has been described mostly in bacteria, this survival skill is widespread, including in eukaryotic microorganisms. In Leishmania, a digenetic parasitic protozoan that causes a major infectious disease, quiescence has been demonstrated, but molecular and metabolic features enabling its maintenance are unknown. Here we quantified the transcriptome and metabolome of Leishmania promastigotes and amastigotes where quiescence was induced in vitro either through drug pressure or by stationary phase. Quiescent cells have a global and coordinated reduction in overall transcription, with levels dropping to as low as 0.4% of those in proliferating cells. However, a subset of transcripts did not follow this trend and were relatively upregulated in quiescent populations, including those encoding membrane components such as amastins and GP63 or processes like autophagy. The metabolome followed a similar trend of overall downregulation albeit to a lesser magnitude than the transcriptome. Noteworthy, among the commonly upregulated metabolites were those involved in carbon sources as an alternative to glucose. This first integrated two omics layers affords novel insights into cell regulation and shows commonly modulated features across stimuli and stages.

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“…The ALSP has been purified previously and found to be a lipase (Pre-print). It is expressed specifically in the amastigote stage indicating its probable role in visceralisation [37]. Acid ecto-phosphatases, a member of Histidine Acid Phosphatase have been reported to confer resistance to oxidative stress by inhibiting Neutrophil superoxide anion production [38].…”

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confidence: 99%

In-silico design of an immunoinformatics based multi-epitope vaccine against Leishmania donovani

et al. 2022

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Background Visceral Leishmaniasis (VL) is a fatal vector-borne parasitic disorder occurring mainly in tropical and subtropical regions. VL falls under the category of neglected tropical diseases with growing drug resistance and lacking a licensed vaccine. Conventional vaccine synthesis techniques are often very laborious and challenging. With the advancement of bioinformatics and its application in immunology, it is now more convenient to design multi-epitope vaccines comprising predicted immuno-dominant epitopes of multiple antigenic proteins. We have chosen four antigenic proteins of Leishmania donovani and identified their T-cell and B-cell epitopes, utilizing those for in-silico chimeric vaccine designing. The various physicochemical characteristics of the vaccine have been explored and the tertiary structure of the chimeric construct is predicted to perform docking studies and molecular dynamics simulations. Results The vaccine construct is generated by joining the epitopes with specific linkers. The predicted tertiary structure of the vaccine has been found to be valid and docking studies reveal the construct shows a high affinity towards the TLR-4 receptor. Population coverage analysis shows the vaccine can be effective on the majority of the world population. In-silico immune simulation studies confirms the vaccine to raise a pro-inflammatory response with the proliferation of activated T and B cells. In-silico codon optimization and cloning of the vaccine nucleic acid sequence have also been achieved in the pET28a vector. Conclusion The above bioinformatics data support that the construct may act as a potential vaccine. Further wet lab synthesis of the vaccine and in vivo works has to be undertaken in animal model to confirm vaccine potency.

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Characterization of a novel amastin-like surface protein (ALSP) ofLeishmania donovani, a probable lipase

Cited by 5 publications

References 62 publications

Transcriptional Shift and Metabolic Adaptations during Leishmania Quiescence Using Stationary Phase and Drug Pressure as Models

Transcriptional Shift and Metabolic Adaptations during Leishmania Quiescence Using Stationary Phase and Drug Pressure as Models

Transcriptional shift and metabolic adaptations during Leishmania quiescence using stationary-phase and drug pressure as models

In-silico design of an immunoinformatics based multi-epitope vaccine against Leishmania donovani

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