Trypanosoma brucei: Metabolomics for analysis of cellular metabolism and drug discovery

被引:10
作者
Fall, Fanta [1 ]
Mamede, Lucia [2 ]
Schioppa, Laura [1 ]
Ledoux, Allison [2 ]
De Tullio, Pascal [3 ]
Michels, Paul [4 ,5 ]
Frederich, Michel [2 ]
Quetin-Leclercq, Joelle [1 ]
机构
[1] UCLouvain, Pharmacognosy Res Grp, Louvain Drug Res Inst LDRI, Ave E Mounier B1 72-03, B-1200 Brussels, Belgium
[2] Univ Liege, Ctr Interdisciplinary Res Med CIRM, Lab Pharmacognosy, Liege, Belgium
[3] Univ Liege, Ctr Interdisciplinary Res Med CIRM, Metabol Grp, Liege, Belgium
[4] Univ Edinburgh, Sch Biol Sci, Ctr Immun Infect & Evolut CIIE, Edinburgh, Midlothian, Scotland
[5] Univ Edinburgh, Sch Biol Sci, Ctr Translat & Chem Biol CTCB, Edinburgh, Midlothian, Scotland
关键词
Metabolomics; Anti-trypanosomal activity; Trypanosoma brucei; Mass spectrometry; Nuclear magnetic resonance; BLOOD-STREAM FORMS; N-MYRISTOYLTRANSFERASE INHIBITORS; AFRICAN TRYPANOSOMIASIS; SLEEPING SICKNESS; LIPID-METABOLISM; GUIDED ISOLATION; PROCYCLIC FORM; IDENTIFICATION; BIOLOGY; MELARSOPROL;
D O I
10.1007/s11306-022-01880-0
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background Trypanosoma brucei is the causative agent of Human African Trypanosomiasis (also known as sleeping sickness), a disease causing serious neurological disorders and fatal if left untreated. Due to its lethal pathogenicity, a variety of treatments have been developed over the years, but which have some important limitations such as acute toxicity and parasite resistance. Metabolomics is an innovative tool used to better understand the parasite's cellular metabolism, and identify new potential targets, modes of action and resistance mechanisms. The metabolomic approach is mainly associated with robust analytical techniques, such as NMR and Mass Spectrometry. Applying these tools to the trypanosome parasite is, thus, useful for providing new insights into the sleeping sickness pathology and guidance towards innovative treatments. Aim of review The present review aims to comprehensively describe the T. brucei biology and identify targets for new or commercialized antitrypanosomal drugs. Recent metabolomic applications to provide a deeper knowledge about the mechanisms of action of drugs or potential drugs against T. brucei are highlighted. Additionally, the advantages of metabolomics, alone or combined with other methods, are discussed. Key scientific concepts of review Compared to other parasites, only few studies employing metabolomics have to date been reported on Trypanosoma brucei. Published metabolic studies, treatments and modes of action are discussed. The main interest is to evaluate the metabolomics contribution to the understanding of T. brucei's metabolism.
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页数:18
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