Shape, form, function and Leishmania pathogenicity: from textbook descriptions to biological understanding

Abstract

The shape and form of protozoan parasites are inextricably linked to their pathogenicity. The evolutionary pressure associated with establishing and maintaining an infection and transmission to vector or host has shaped parasite morphology. However, there is not a 'one size fits all' morphological solution to these different pressures, and parasites exhibit a range of different morphologies, reflecting the diversity of their complex life cycles. In this review, we will focus on the shape and form of Leishmania spp., a group of very successful protozoan parasites that cause a range of diseases from self-healing cutaneous leishmaniasis to visceral leishmaniasis, which is fatal if left untreated.

Keywords: Leishmania; morphology; parasite; pathogenicity.

Figure 1.

Schematic of promastigote and amastigote morphologies and the Leishmania life cycle with the different cell types highlighted. (a) Promastigote and amastigote morphologies aligned along the posterior anterior axis with key structures in the cells indicated. (b) Cartoon of the current understanding of the Leishmania life cycle with critical events and different cell types highlighted. A sand fly takes a blood meal from an infected mammalian host and ingests a macrophage containing Leishmania amastigotes. Once in the sand fly midgut, the amastigotes differentiate into procyclic promastigotes. Next, the procyclic promastigotes become nectomonad promastigotes, which escape the peritrophic matrix and then attach to the microvilli in the midgut before moving to the thoracic midgut and stomodeal valve where they differentiate into leptomonad promastigotes. Here, the leptomonad promastigotes differentiate into either haptomonad promastigotes which attach to the stomodeal valve or metacyclic promastigotes that are the mammalian infective form, which are transmitted when the sand fly next takes a blood meal. Proliferative stages are indicated by a circular arrow.

Figure 2.

Development of Leishmania in the sand fly digestive tract. (a) Illustrations of the major promastigote morphologies observed in the sand fly during a Leishmania infection. (b) Leishmania cell number per sand fly during a typical sand fly infection over the course of 10 days. (c) Cell density from (b) was re-plotted and the doubling times calculated for the early and late infection stages. (d) Analysis of the proportions of different cell types observed during a sand fly infection. (a), (b) and (d) are reproduced with permission from Rogers et al. [86]. (e) Schematic of Leishmania cell cycle with the corresponding cell types shown above. (f) Correlation of flagellum and cell body length from three independent L. mexicana in vitro cultures analysed at different cell densities. The data were then subsequently classified into the different promastigote morphologies [86]. (g) Proportion of cells with different promastigote morphology by cell cycle progress. The cell cycle progress of the cells used in the analysis for (f) was calculated based on their cell length and DNA content and then combined with the promastigote morphology classification from (f) [87,88]. Dotted lines indicate transitions between cell cycle stages (C, cytokinesis). (e) and (f) are reproduced with permission from Wheeler [89].