Developmental differentiation in Leishmania lifecycle progression: post-transcriptional control conducts the orchestra

Pablos, LM De; Ferreira, TR; Walrad, Pegine

doi:10.1016/j.mib.2016.08.004

Cited by 53 publications

(62 citation statements)

References 59 publications

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“…The main life stages of Leishmania , procyclic and metacyclic promastigotes and amastigotes, display differences in the abundance and profile of essential molecules, reflecting adaptations to different environmental conditions. Nonreplicative metacyclic promastigotes show a 4–6‐fold reduction of RNA, protein and lipids compared to procyclic promastigotes, and the two stages have up to 30% differentially expressed transcripts . However, the role of mRNA regulation in protein abundance during Leishmania development is still controversial.…”

Section: Potential Applications Of Proteomics In Leishmaniasismentioning

confidence: 99%

Proteomics and Leishmaniasis: Potential Clinical Applications

Capelli-Peixoto

Mule

Tano

et al. 2019

Proteomics Clinical Apps

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Leishmaniases are diseases caused by protozoan parasites of the genus Leishmania. They are endemic in 98 countries, affect around 12 million people worldwide and may present several distinct clinical forms. Unfortunately, there are only a few drugs available for treatment of leishmaniasis, which are toxic and not always effective. Different parasite species and different clinical forms require optimization of the treatment or more specific therapies, which are not available. The emergence of resistance is also a matter of concern. Besides, diagnosis can sometimes be complicated due to atypical manifestations and associations with other pathologies. In this review, proteomic data are presented and discussed in terms of their application in important issues in leishmaniasis such as parasite resistance to chemotherapy, diagnosis of active disease in patients and dogs, markers for different clinical forms, identification of virulence factors, and their potential use in vaccination. It is shown that proteomics has contributed to the discovery of potential biomarkers for prognosis, diagnosis, therapeutics, monitoring of disease progression, treatment follow‐up and identification of vaccine candidates for specific diseases. However, the authors believe its capabilities have not yet been fully explored for routine clinical analysis for several reasons, which will be presented in this review.

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Section: Potential Applications Of Proteomics In Leishmaniasismentioning

confidence: 99%

Proteomics and Leishmaniasis: Potential Clinical Applications

Capelli-Peixoto

Mule

Tano

et al. 2019

Proteomics Clinical Apps

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“…These protozoa have a dixenous lifecycle that transitions between multiple promastigote stages in the sandfly vector . to the amastigote stage in the phagolysosomes of mammalian immune cells [2]. Distinct environmental conditions (pH, temperature, nutrient availability) serve as triggers for developmental events.…”

Section: Introductionmentioning

confidence: 99%

“…Distinct environmental conditions (pH, temperature, nutrient availability) serve as triggers for developmental events. For parasite lifecycle progression, both metacyclogenesis (procyclic to metacyclic promastigote) and amastigogenesis (metacyclic promastigote to amastigote) differentiation processes require tightly coordinated gene regulation [2]. To date, many ciselements but strikingly few trans-regulators have been implicated in Leishmania developmental progression [3][4][5][6][7][8][9][10][11].…”

Section: Introductionmentioning

confidence: 99%

The mRNA-bound proteome ofLeishmania mexicana: novel genetic insight into an ancient parasite

Pablos

Ferreira

Dowle

et al. 2019

Preprint

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Leishmania parasite infections, termed the leishmaniases, cause significant global infectious disease burden. The lifecycle of the parasite embodies three main stages that require precise coordination of gene regulation to survive environmental shifts between sandfly and mammalian hosts. Constitutive transcription in kinetoplastid parasites means that gene regulation is overwhelmingly reliant on post-transcriptional mechanisms, yet strikingly few Leishmania trans-regulators are known. Utilizing optimised crosslinking and deep, quantified mass spectrometry, we present a comprehensive analysis of 1,400 mRNA binding proteins (mRBPs) and whole cell proteomes from the three main Leishmania lifecycle stages.Supporting the validity, while the crosslinked RBPome is magnitudes more enriched the protein identities of the crosslinked and non-crosslinked RBPomes were nearly identical.Moreover, multiple candidate RBPs were endogenously tagged and found to associate with discrete mRNA target pools in a stage-specific manner. Results indicate that in L.mexicana parasites, mRNA levels are not a strong predictor of the whole cell expression or RNA binding potential of encoded proteins. Evidence includes a low correlation between transcript and corresponding protein expression and stage-specific variation in protein expression versus RNA binding potential. Unsurprisingly, RNA binding protein enrichment correlates strongly with relative replication efficiency of the specific lifecycle stage. Our study is the first to quantitatively define and compare the mRBPome of multiple stages in kinetoplastid parasites. It provides novel, in-depth insight into the trans-regulatory mRNA:Protein (mRNP) complexes that drive Leishmania parasite lifecycle progression.

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“…The cells are motile, and swim with the aid of a narrow, whip-like organelle known as a flagellum at the leading end of the more substantial cell body. The flagellum is of order 10 m in length when a cell is motile, but this varies significantly over the course of the life cycle, which also includes non-motile stages [38]. The diameter of the flagellum varies much less, and is roughly 400 nm [39] during motile stages.…”

Section: Introductionmentioning

confidence: 99%

Simultaneous two-color imaging in digital holographic microscopy

et al. 2017

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Abstract:We demonstrate the use of two-color digital holographic microscopy (DHM) for imaging microbiological subjects. The use of two wavelengths significantly reduces artifacts present in the reconstructed data, allowing us to image weakly-scattering objects in close proximity to strongly-scattering objects. We demonstrate this by reconstructing the shape of the flagellum of a unicellular eukaryotic parasite Leishmania mexicana in close proximity to a more strongly-scattering cell body. Our approach also yields a reduction of approximately one third in the axial position uncertainty when tracking the motion of swimming cells at low magnification, which we demonstrate with a sample of Escherichia coli bacteria mixed with polystyrene beads. The two-wavelength system that we describe introduces minimal additional complexity into the optical system, and provides significant benefits.

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Developmental differentiation in Leishmania lifecycle progression: post-transcriptional control conducts the orchestra

Cited by 53 publications

References 59 publications

Proteomics and Leishmaniasis: Potential Clinical Applications

Proteomics and Leishmaniasis: Potential Clinical Applications

The mRNA-bound proteome ofLeishmania mexicana: novel genetic insight into an ancient parasite

Simultaneous two-color imaging in digital holographic microscopy

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