Metabolomic analyses of Leishmania reveal multiple species differences and large differences in amino acid metabolism

Gareth D Westrop, Roderick A M Williams, Lijie Wang, Tong Zhang, David G Watson, Ana Marta Silva, Graham H Coombs

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Comparative genomic analyses of Leishmania species have revealed relatively minor heterogeneity amongst recognised housekeeping genes and yet the species cause distinct infections and pathogenesis in their mammalian hosts. To gain greater information on the biochemical variation between species, and insights into possible metabolic mechanisms underpinning visceral and cutaneous leishmaniasis, we have undertaken in this study a comparative analysis of the metabolomes of promastigotes of L. donovani, L. major and L. mexicana. The analysis revealed 64 metabolites with confirmed identity differing 3-fold or more between the cell extracts of species, with 161 putatively identified metabolites differing similarly. Analysis of the media from cultures revealed an at least 3-fold difference in use or excretion of 43 metabolites of confirmed identity and 87 putatively identified metabolites that differed to a similar extent. Strikingly large differences were detected in their extent of amino acid use and metabolism, especially for tryptophan, aspartate, arginine and proline. Major pathways of tryptophan and arginine catabolism were shown to be to indole-3-lactate and arginic acid, respectively, which were excreted. The data presented provide clear evidence on the value of global metabolomic analyses in detecting species-specific metabolic features, thus application of this technology should be a major contributor to gaining greater understanding of how pathogens are adapted to infecting their hosts.

LanguageEnglish
Article numbere0136891
Number of pages29
JournalPLOS One
Volume10
Issue number9
DOIs
Publication statusPublished - 14 Sep 2015

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Metabolomics
Leishmania
amino acid metabolism
metabolomics
Metabolites
interspecific variation
Metabolism
Tryptophan
metabolites
Amino Acids
Cutaneous Leishmaniasis
Visceral Leishmaniasis
Metabolome
Essential Genes
Cell Extracts
Proline
tryptophan
arginine
Culture Media
Arginine

Keywords

  • Leishmania
  • genes
  • genomic analyses

Cite this

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abstract = "Comparative genomic analyses of Leishmania species have revealed relatively minor heterogeneity amongst recognised housekeeping genes and yet the species cause distinct infections and pathogenesis in their mammalian hosts. To gain greater information on the biochemical variation between species, and insights into possible metabolic mechanisms underpinning visceral and cutaneous leishmaniasis, we have undertaken in this study a comparative analysis of the metabolomes of promastigotes of L. donovani, L. major and L. mexicana. The analysis revealed 64 metabolites with confirmed identity differing 3-fold or more between the cell extracts of species, with 161 putatively identified metabolites differing similarly. Analysis of the media from cultures revealed an at least 3-fold difference in use or excretion of 43 metabolites of confirmed identity and 87 putatively identified metabolites that differed to a similar extent. Strikingly large differences were detected in their extent of amino acid use and metabolism, especially for tryptophan, aspartate, arginine and proline. Major pathways of tryptophan and arginine catabolism were shown to be to indole-3-lactate and arginic acid, respectively, which were excreted. The data presented provide clear evidence on the value of global metabolomic analyses in detecting species-specific metabolic features, thus application of this technology should be a major contributor to gaining greater understanding of how pathogens are adapted to infecting their hosts.",
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Metabolomic analyses of Leishmania reveal multiple species differences and large differences in amino acid metabolism. / Westrop, Gareth D; Williams, Roderick A M; Wang, Lijie; Zhang, Tong; Watson, David G; Silva, Ana Marta; Coombs, Graham H.

In: PLOS One, Vol. 10, No. 9, e0136891, 14.09.2015.

Research output: Contribution to journalArticle

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