Evolutionary comparison of prenylation pathway in kinetoplastid Leishmania and its sister Leptomonas

The information provided about the metabolic pathways modulated when contrasting these two phenotypes may lead to the development of new strategies to block parasite differentiation within the host and to also circumvent the problem of drug resistance. This proteomic study also offers new grounds for the investigation of novel hypothetical proteins potentially playing a role in evolutionary biology the knowledge of which is essential for treatment of patients co-infected with these two kinetoplastid parasites.

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“…According to trypanosomatid phylogeny, Leptomonas spp. are considered as a sister group to the genus Leishmania …”

Section: Resultsmentioning

confidence: 99%

Differential Metabolic Pathway Analysis of the Proteomes of Leishmania donovani and Leptomonas seymouri

Singh

Goel

Jain

2018

Proteomics Clinical Apps

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“…Early descriptions defined Leptomonas as having a life-cycle containing both promastigote and amastigote stages [76], being parasitic only to invertebrates and of no medical importance [77–79]. This system also restricted Leptomonas spp.…”

Section: Problems With Classical Trypanosomatid Systematicsmentioning

confidence: 99%

“…, Calocorisca altiplana , Stenodema andina , Prepops cf. accinctus Trypanosomatids with a life-cycle containing both promastigote- and amastigote stages [76], parasitic only in invertebrates and generally considered of no medical importance [77–79]. However, several reports of Leptomonas seymouri infection in vertebrates have emerged [53].…”

Section: Introductionmentioning

confidence: 99%

The evolution of trypanosomatid taxonomy

Kaufer¹,

Ellis²,

Stark³

et al. 2017

Parasites Vectors

157

114

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Trypanosomatids are protozoan parasites of the class Kinetoplastida predominately restricted to invertebrate hosts (i.e. possess a monoxenous life-cycle). However, several genera are pathogenic to humans, animals and plants, and have an invertebrate vector that facilitates their transmission (i.e. possess a dixenous life-cycle). Phytomonas is one dixenous genus that includes several plant pathogens transmitted by phytophagous insects. Trypanosoma and Leishmania are dixenous genera that infect vertebrates, including humans, and are transmitted by hematophagous invertebrates. Traditionally, monoxenous trypanosomatids such as Leptomonas were distinguished from morphologically similar dixenous species based on their restriction to an invertebrate host. Nonetheless, this criterion is somewhat flawed as exemplified by Leptomonas seymouri which reportedly infects vertebrates opportunistically. Similarly, Novymonas and Zelonia are presumably monoxenous genera yet sit comfortably in the dixenous clade occupied by Leishmania. The isolation of Leishmania macropodum from a biting midge (Forcipomyia spp.) rather than a phlebotomine sand fly calls into question the exclusivity of the Leishmania-sand fly relationship, and its suitability for defining the Leishmania genus. It is now accepted that classic genus-defining characteristics based on parasite morphology and host range are insufficient to form the sole basis of trypanosomatid taxonomy as this has led to several instances of paraphyly. While improvements have been made, resolution of evolutionary relationships within the Trypanosomatidae is confounded by our incomplete knowledge of its true diversity. The known trypanosomatids probably represent a fraction of those that exist and isolation of new species will help resolve relationships in this group with greater accuracy. This review incites a dialogue on how our understanding of the relationships between certain trypanosomatids has shifted, and discusses new knowledge that informs the present taxonomy of these important parasites.

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“…Protein isoprenylation system of invertebrates is operative in phylogenetically diverse organisms, and its components are often exchangeable . Hence, novel insights in prenylation‐driven elements of invertebrate viral lifecycles may be relevant to human viruses.…”

Section: Prenylation Is Common In Proteins Encoded By Diverse Groups mentioning

confidence: 99%

Prenylation of viral proteins by enzymes of the host: Virus‐driven rationale for therapy with statins and FT/GGT1 inhibitors

et al. 2017

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Intracellular bacteria were recently shown to employ eukaryotic prenylation system for modifying activity and ensuring proper intracellular localization of their own proteins. Following the same logic, the proteins of viruses may also serve as prenylation substrates. Using extensively validated high‐confidence prenylation predictions by PrePS with a cut‐off for experimentally confirmed farnesylation of hepatitis delta virus antigen, we compiled in silico evidence for several new prenylation candidates, including IRL9 (CMV) and few other proteins encoded by Herpesviridae, Nef (HIV‐1), E1A (human adenovirus 1), NS5A (HCV), PB2 (influenza), HN (human parainfluenza virus 3), L83L (African swine fever), MC155R (molluscum contagiosum virus), other Poxviridae proteins, and some bacteriophages of human associated bacteria. If confirmed experimentally, these findings may aid in dissection of molecular functions of uncharacterized viral proteins and provide a novel rationale for statin and FT/GGT1‐based inhibition of viral infections. Prenylation of bacteriophage proteins may aid in moderation of microbial infections. Also see the video abstract here: https://youtu.be/0qVW3ym1R1g

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Evolutionary comparison of prenylation pathway in kinetoplastid Leishmania and its sister Leptomonas

Cited by 10 publications

References 59 publications

Differential Metabolic Pathway Analysis of the Proteomes of Leishmania donovani and Leptomonas seymouri

Differential Metabolic Pathway Analysis of the Proteomes of Leishmania donovani and Leptomonas seymouri

The evolution of trypanosomatid taxonomy

Prenylation of viral proteins by enzymes of the host: Virus‐driven rationale for therapy with statins and FT/GGT1 inhibitors

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