Leishmania Encodes a Bacterium-like 2,4-Dienoyl-Coenzyme A Reductase That Is Required for Fatty Acid β-Oxidation and Intracellular Parasite Survival

Author:

Semini Geo1,Paape Daniel23,Blume Martin45,Sernee M. Fleur5,Peres-Alonso Diego16,Calvignac-Spencer Sébastien7,Döllinger Jörg8,Jehle Stefan9,Saunders Eleanor5,McConville Malcolm J.5,Aebischer Toni12

Affiliation:

1. Mycotic and Parasitic Agents and Mycobacteria (FG16), Department of Infectious Diseases, Robert Koch Institute, Berlin, Germany

2. Institute of Immunology and Infection Research, The University of Edinburgh, Edinburgh, United Kingdom

3. Wellcome Centre for Integrative Parasitology, University of Glasgow, Glasgow, United Kingdom

4. Metabolism of Microbial Pathogens (NG2), Robert Koch Institute, Berlin, Germany

5. Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, Victoria, Australia

6. Departamento de Parasitologia, Instituto de Biociências, Universidade Estadual Paulista, Botucatu, SP, Brazil

7. Epidemiology of Highly Pathogenic Microorganisms, Robert Koch Institute, Berlin, Germany

8. Proteomics and Spectroscopy (ZBS 6), Robert Koch Institute, Berlin, Germany

9. Department of NMR-supported Structural Biology, Leibniz-Institute for Molecular Pharmacology, Berlin, Germany

Abstract

The Trypanosomatidae are protozoan parasites that infect insects, plants, and animals and have evolved complex monoxenous (single host) and dixenous (two hosts) lifestyles. A number of species of Trypanosomatidae, including Leishmania spp., have evolved the capacity to survive within intracellular niches in vertebrate hosts. The adaptations, metabolic and other, that are associated with development of intracellular lifestyles remain poorly defined. We show that genomes of Leishmania and Trypanosomatidae that can survive intracellularly encode a 2,4-dienoyl-CoA reductase that is involved in catabolism of a subclass of fatty acids. The trypanosomatid enzyme shows closest similarity to the corresponding bacterial enzymes and is located in the mitochondrion and essential for intracellular growth of Leishmania . The findings suggest that acquisition of this gene by lateral gene transfer from bacteria by ancestral monoxenous Trypanosomatidae likely contributed to the development of a dixenous lifestyle of these parasites.

Funder

German Ministry of Education and Research

Deutsche Forschungsgemeinschaft

European Commission

Publisher

American Society for Microbiology

Subject

Virology,Microbiology

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