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Comparative sphingolipidomics of disease-causing trypanosomatids reveal unique lifecycle- and taxonomy-specific lipid chemistries.

ABSTRACT: Trypanosomatids are parasitic protozoa which cause a spectrum of diseases, including trypanosomiasis and leishmaniasis, affecting millions of humans and animals worldwide. The surface of most protozoan parasites is heavily decorated with lipids and lipid-anchored molecules, forming protective barriers and acting as virulence factors during infection. Sphingolipids (SP) are major components of eukaryotic biomembranes, which play important roles in structural integrity, energy homeostasis and signaling. However, the precise chemical composition of SP in pathogens as well as their biochemical pathways and functions remain poorly characterized. Here, we present the first system-scale analyses of SP found in a panel of 7 trypanosomatids, including Leishmania donovani, Trypanosoma brucei and Trypanosoma cruzi. We characterized the structure of aminoethylphosphonate-containing ceramides, which are found exclusively in stercorarian Trypanosoma. Employing the sensitive and semi-quantitative sphingolipidomics approach that we developed, we report the detection of over 300 molecular species of SP, and identified unique metabolic signatures which serve as discriminants of the pathogens based on their taxonomy and lifecycle stages. The deep sphingolipidome presented here is an important biochemical and technological resource for future works to dissect SP metabolism and functions in these medically and agriculturally relevant systems.

SUBMITTER: Guan XL

PROVIDER: S-EPMC5648825 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Comparative sphingolipidomics of disease-causing trypanosomatids reveal unique lifecycle- and taxonomy-specific lipid chemistries.

Guan Xue Li XL Mäser Pascal P

Scientific reports 20171019 1

Trypanosomatids are parasitic protozoa which cause a spectrum of diseases, including trypanosomiasis and leishmaniasis, affecting millions of humans and animals worldwide. The surface of most protozoan parasites is heavily decorated with lipids and lipid-anchored molecules, forming protective barriers and acting as virulence factors during infection. Sphingolipids (SP) are major components of eukaryotic biomembranes, which play important roles in structural integrity, energy homeostasis and sign ...[more]

PMID: 29051559

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Project description:BackgroundRecent studies have provided extensive evidence for multitudes of non-coding RNA (ncRNA) transcripts in a wide range of eukaryotic genomes. ncRNAs are emerging as key players in multiple layers of cellular regulation. With the availability of many whole genome sequences, comparative analysis has become a powerful tool to identify ncRNA molecules. In this study, we performed a systematic genome-wide in silico screen to search for novel small ncRNAs in the genome of Trypanosoma brucei using techniques of comparative genomics.ResultsIn this study, we identified by comparative genomics, and validated by experimental analysis several novel ncRNAs that are conserved across multiple trypanosomatid genomes. When tested on known ncRNAs, our procedure was capable of finding almost half of the known repertoire through homology over six genomes, and about two-thirds of the known sequences were found in at least four genomes. After filtering, 72 conserved unannotated sequences in at least four genomes were found, 29 of which, ranging in size from 30 to 392 nts, were conserved in all six genomes. Fifty of the 72 candidates in the final set were chosen for experimental validation. Eighteen of the 50 (36%) were shown to be expressed, and for 11 of them a distinct expression product was detected, suggesting that they are short ncRNAs. Using functional experimental assays, five of the candidates were shown to be novel H/ACA and C/D snoRNAs; these included three sequences that appear as singletons in the genome, unlike previously identified snoRNA molecules that are found in clusters. The other candidates appear to be novel ncRNA molecules, and their function is, as yet, unknown.ConclusionsUsing comparative genomic techniques, we predicted 72 sequences as ncRNA candidates in T. brucei. The expression of 50 candidates was tested in laboratory experiments. This resulted in the discovery of 11 novel short ncRNAs in procyclic stage T. brucei, which have homologues in the other trypansomatids. A few of these molecules are snoRNAs, but most of them are novel ncRNA molecules. Based on this study, our analysis suggests that the total number of ncRNAs in trypanosomatids is in the range of several hundred.

Dataset Information

Comparative sphingolipidomics of disease-causing trypanosomatids reveal unique lifecycle- and taxonomy-specific lipid chemistries.

Publications

Comparative sphingolipidomics of disease-causing trypanosomatids reveal unique lifecycle- and taxonomy-specific lipid chemistries.

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