How apicomplexans are pulling the strings behind the scenes to make the best out of their parasitic life style
The latest Parasitology Paper of the Month is “Apicomplexans pulling the strings: manipulation of the host cell cytoskeleton dynamics” by Rita Cardoso, Helena Soares, Andrew Hemphill and Alexandre Leitão.
The cytoskeleton is a complex filamentous network of microtubules, actin microfilaments and intermediate filaments. This network is involved in many cellular activities, including the maintenance of cell shape, positioning of intracellular organelles, intracellular cargo transportation, cell division and motility. With this in mind, it is not surprising that invasive pathogens, once they reach the interior of their host cell, modulate host cell cytoskeletal dynamics and structures to create a compartment that fulfils their own requirements. This is also true for apicomplexan parasites, a diverse group of intracellular pathogens of medical and veterinary importance. Some life cycle stages of apicomplexans (e.g. Toxoplasma) are capable of infecting many different hosts and can exploit a wide range of host cell types, while others (e.g. Plasmodium, Theileria, Babesia, Cryptosporidium, Eimeira) are confined to specific tissues and cell types, and exhibit a rather narrow host range. It is thus conceivable that there are distinct strategies in how the different species manipulate the host cell cytoskeleton. However, even phylogenetically closely related cyst-forming coccidia such as Toxoplasma and Besnoitia, differentially interact with the host cell cytoskeleton.
Besnoitia besnoiti and Toxoplasma gondii cause high economical losses in animal production: besnoitiosis affects milk production in cattle, can cause abortion, transient or permanent infertility of bulls, and severe skin lesions; toxoplasmosis is one of the main causes of abortion, fetal mummification, stillbirth and neonatal mortality in sheep and goats. Both parasites are of veterinary importance, and T. gondii is also of high medical relevance,as acute infections are a concern in human medicine, particularly during pregnancy and in immune-compromised individuals.
As intracellular parasites, B. besnoiti and T. gondii interact with, and modify, certain host cell elements. We have observed a rearrangement of the host cell microtubules not only during the initial steps of host cell invasion by B. besnoiti and T. gondii, but also during parasitophorous vacuole establishment and parasite replication. However, they differ in the rearrangement they induce: in cells infected with replicating B. besnoiti tachyzoites, the microtubules present a complex arrangement around the parasitophorous vacuole, creating an alveolus-like structure; T. gondii infected host cells exhibit a basket-like structure. Also, for T. gondii, but not for B. besnoiti the interaction with the host microtubules implicates the recruitment of the host cell centrosome. Clearly, B. besnoiti has developed a different strategy to invade and replicate in host cells that does not require centrosomes of the host nearby the parasitophorous vacuole. These apparently different methods of exploring the host cell microtubule cytoskeleton was a quite exciting finding that motivated us to review the modulation of cytoskeletal elements in cells infected by other apicomplexans, such as Plasmodium spp., Neospora caninum, Cryptosporidium spp., Theileria spp. and Babesia spp.. This paper assembles the available information on pathways, molecular targets, and overall different strategies employed by apicomplexans, with the purpose to shed light on how apicomplexans are pulling the strings behind the scenes to make the best out of their parasitic life style. All together, these data can help us to understand the molecular mechanisms underlying intracellular survival that might be crucial for defining prophylactic and therapeutic strategies.
Read the review paper “Apicomplexans pulling the strings: manipulation of the host cell cytoskeleton dynamics” in full for free until 30th August 2016.