Dictyostelium discoideum as a non-mammalian biomedical model

Abstract

Dictyostelium discoideum is one of eight non-mammalian model organisms recognized by the National Institute of Health for the study of human pathology. The use of this slime mould is possible owing to similarities in cell structure, behaviour and intracellular signalling with mammalian cells. Its haploid set of chromosomes completely sequenced amenable to genetic manipulation, its unique and short life cycle with unicellular and multicellular stages, and phenotypic richness encoding many human orthologues, make Dictyostelium a representative and simple model organism to unveil cellular processes in human disease. Dictyostelium studies within the biomedical field have provided fundamental knowledge in the areas of bacterial infection, immune cell chemotaxis, autophagy/phagocytosis and mitochondrial and neurological disorders. Consequently, Dictyostelium has been used to the development of related pharmacological treatments. Herein, we review the utilization of Dictyostelium as a model organism in biomedicine.

Fig. 1

Dictyostelium cells (A) and developmental time course (B, C, D) in the absence of nutrients. Wild‐type AX3 cells grown in shaking axenic culture were plated on glass (A), and on non‐nutrient agar plates (B, C, D) and allowed to starve (t = 0 h) as previously described (Lacal et al., 2018). (A) Image of AX3 cells plated on glass by digital interference contrast microscopy. In the absence of nutrients starvation is imminent, the amoebae stop dividing and activate several genes that will allow them to aggregate by chemotaxis towards cAMP diffusing from centrally located cells. Pictures of developing cells were taken during (B) aggregation (t = 6 h), (C) mound (t = 12 h) and (D) after completion of formation of fruiting bodies (t = 24 h) using time‐lapse phase‐contrast microscopy. Scale bar in (A), 50 µm, whereas in (B, C, D) represents 1 mm.

Fig. 2

D. discoideum genes with implications in pathogenesis. A total of 29 genes have been identified in Dictyostelium as host model for pathogenesis. The encoded proteins are involved in intracellular growth (blue), bacterial uptake (yellow) and in both processes (overlapping area).

Fig. 3

D. discoideum genes implicated in neurological disorders. This Venn diagram includes some of the most interesting genes in D. discoideum for the study of neurological diseases in humans including Alzheimer, Huntington, epilepsy, neuronal ceroid lipofuscinosis and bipolar disorder. *ino1 is also related with bipolar disease which is not represented in the figure.

Fig. 4

Biological implications of Dictyostelium discoideum proteins according to the different fields reported in this review. The six most significant GO terms for biological processes (by P‐value, and avoiding redundancy) are represented based on their functional annotation of human Uniprot IDs with DAVID 6.7 (Huang et al., 2009, 2009,2009, 2009). Numbers indicate the proteins associated with each biological function. For further detailed information, please refer to Table S6.