Abstract
Pleomorphic Trypanosoma brucei are best known for their tightly controlled cell growth and developmental program, which ensures their transmissibility and host fitness between the mammalian host and insect vector. However, after long-term adaptation in the laboratory or by natural evolution, monomorphic parasites can be derived. The origin of these monomorphic forms is currently unclear. Here, we produced a series of monomorphic trypanosome stocks by artificially syringe-passage in mice, creating snapshots of the transition from pleomorphism to monomorphism. We then compared these artificial monomorphic trypanosomes, alongside several naturally monomorphic T. evansi and T. equiperdum strains, with the pleomorphic T. brucei. In addition to failing to generate stumpy forms in animal bloodstream, we found that monomorphic trypanosomes from laboratory and nature exhibited distinct differentiation patterns, which are reflected by their distinct differentiation potential and transcriptional changes. Lab-adapted monomorphic trypanosomes could still be induced to differentiate, and showed only minor transcriptional differences to that of the pleomorphic slender forms but some accumulated differences were observed as the passages progress. All naturally monomorphic strains completely fail to differentiate, corresponding to their impaired differentiation regulation. We propose that the natural phenomenon of trypanosomal monomorphism is actually a malignant manifestation of protozoal cells. From a disease epidemiological and evolutionary perspective, our results provide evidence for a new way of thinking about the origin of these naturally monomorphic strains, the malignant evolution of trypanosomes may raise some concerns. Additionally, these monomorphic trypanosomes may reflect the quantitative and qualitative changes in the malignant evolution of T. brucei, suggesting that single-celled protozoa may also provide the most primitive model of cellular malignancy, which could be a primitive and inherent biological phenomenon of eukaryotic organisms from protozoans to mammals.
Highlights
Trypanosoma brucei has a complicated life cycle, with multiple differentiation and multiplication events in both the mammalian host and the insect vector, which limits its distribution in Africa to where the tsetse fly vector is present (Wijers, 1959; Vickerman, 1965)
Cell differentiation is a typical characteristic of eukaryotic organisms from protozoans to mammals and, FIGURE 7 | Relationships between differentiation potential of different trypanosomes and the expression of the selected differentiation characteristic transcripts (DCTs)
It is seen in protozoans with complicated life cycles, such as Trypanosoma brucei, the pathogen causing African human sleeping sickness or Nagana disease in livestock and wild mammals (Cayla et al, 2019)
Summary
Trypanosoma brucei has a complicated life cycle, with multiple differentiation and multiplication events in both the mammalian host and the insect vector (pleomorphism), which limits its distribution in Africa to where the tsetse fly vector is present (Wijers, 1959; Vickerman, 1965). Based on a large number of biological and genomic characteristics of these parasitic protozoa and a comparison with characteristics of malignant tumor cells (Sachs, 1986; Tenen, 2003; Murgia et al, 2006; Rebbeck et al, 2009; Hanahan and Weinberg, 2011; Carnes et al, 2015), it has been suggested that T. evansi and T. equiperdum originated as the result of malignancy in T. brucei cells that are found in nature (Lun et al, 2015). It has not been systematically established whether this phenomenon of malignancy is widespread in singlecelled protozoa, represented by trypanosomes, and, if so, how such malignancy is triggered
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