‘Disc-o-Fever’: Getting Down with Giardia’s Groovy Microtubule Organelle

Nosala, Christopher; Hagen, Kari D.; Dawson, Scott C.

doi:10.1016/j.tcb.2017.10.007

Cited by 35 publications

(81 citation statements)

References 78 publications

(108 reference statements)

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“…Similar to metazoans, protozoans can also contain unique assemblies of microtubules, such as those making up the suction disc of the intestinal parasite Giardia lamblia (Nosala et al , ) or the axopodia of the free‐living heliozoan Echinosphaerium nucleofilum (Tilney & Porter, ). Key protozoan organisms that are intensely investigated for their diverse biology and medical relevance include the parasites Trypanosoma brucei causing sleeping sickness and various species of Plasmodium , the causative agents of malaria.…”

Section: Introductionmentioning

confidence: 99%

Microtubule number and length determine cellular shape and function in Plasmodium

et al. 2019

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Microtubules are cytoskeletal filaments essential for many cellular processes, including establishment and maintenance of polarity, intracellular transport, division and migration. In most metazoan cells, the number and length of microtubules are highly variable, while they can be precisely defined in some protozoan organisms. However, in either case the significance of these two key parameters for cells is not known. Here, we quantitatively studied the impact of modulating microtubule number and length in Plasmodium , the protozoan parasite causing malaria. Using a gene deletion and replacement strategy targeting one out of two α‐tubulin genes, we show that chromosome segregation proceeds in the oocysts even in the absence of microtubules. However, fewer and shorter microtubules severely impaired the formation, motility and infectivity of Plasmodium sporozoites, the forms transmitted by the mosquito, which usually contain 16 microtubules. We found that α‐tubulin expression levels directly determined the number of microtubules, suggesting a high nucleation barrier as supported by a mathematical model. Infectious sporozoites were only formed in parasite lines featuring at least 10 microtubules, while parasites with 9 or fewer microtubules failed to transmit.

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Section: Introductionmentioning

confidence: 99%

Microtubule number and length determine cellular shape and function in Plasmodium

et al. 2019

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“…intestinalis is not known to possess classical virulence factors, such as 264 enterotoxins, but several genes are important for colonization of the host and thus for 265 pathogenesis. These include genes for motility 10 , the adhesive disc for attachment 9 , 266 secreted cysteine proteases that can degrade host defensive factors 12,13 , and cysteine-rich surface protein like the VSPs 51 and the HCMPs 48 that undergo antigenic variation. The 268 cytoskeletal protein repertoire in G. muris is very similar to G. intestinalis apart from 269 several fragmented alpha-tubulins (3 complete genes with homologs in G. intestinalis and 270 9 incomplete gene fragments).…”

Section: Virulence Factors In Giardia 263mentioning

confidence: 99%

“…Giardia parasites essential for attachment of the trophozoite in the small intestine, but is 272 missing in other fornicates 9 . The first detailed studies of the adhesive disc were performed 273 on G. muris trophozoites 24 , but more recent work has mostly focused on G. intestinalis.…”

Section: Virulence Factors In Giardia 263mentioning

confidence: 99%

“…The vast majority (82 of 85) of G. intestinalis disc proteins 9 were also identified in G. 275 muris (Table S1D); 12 were NEK kinases and 27 were ARP-1 proteins. Two of the three 276 G. intestinalis disc proteins not found in G. muris (Table S1D) localize to a structure in 277 the G. intestinalis disc on top of the ventral groove, but this structure is missing in the G. 278 muris disc 22 , suggesting functional disc differences.…”

Section: Virulence Factors In Giardia 263mentioning

confidence: 99%

“…the Giardia genomes 50 . The Giardia NEK kinases lack transmembrane domains and 454 have been suggested to target and localize to different intracellular structures with 455 their ankyrin repeats 50 and many of the G. intestinalis NEK kinases localize to 456 cytoskeletal structures, including the flagella and adhesive disc 9 . Rearrangements and 457 duplications in the G. muris genome are frequently associated with these large gene 458 families ( Fig.…”

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The compact genome ofGiardia murisreveals important steps in the evolution of intestinal protozoan parasites

Jiménez-González

Einarsson

et al. 2019

Preprint

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AbstractDiplomonad parasites of the genus Giardia have adapted to colonizing different hosts, most notably the intestinal tract of mammals. The human-pathogenic Giardia species, Giardia intestinalis, has been extensively studied at the genome and gene expression level, but no such information is available for other Giardia species. Comparative data would be particularly valuable for Giardia muris, which colonizes mice and is commonly used as a prototypic in vivo model for investigating host responses to intestinal parasitic infection. Here we report the draft-genome of G. muris. We discovered a highly streamlined genome, amongst the most densely encoded ever described for a nuclear eukaryotic genome. G. muris and G. intestinalis share many known or predicted virulence factors, including cysteine proteases and a large repertoire of cysteine-rich surface proteins involved in antigenic variation. Different to G. intestinalis, G. muris maintains tandem arrays of pseudogenized surface antigens at the telomeres, whereas intact surface antigens are present centrally in the chromosomes. The two classes of surface antigens engage in genetic exchange. Reconstruction of metabolic pathways from the G. muris genome suggest significant metabolic differences to G. intestinalis. Additionally, G. muris encodes proteins that might be used to modulate the prokaryotic microbiota. The responsible genes have been introduced in the Giardia genus via lateral gene transfer from prokaryotic sources. Our findings point to important evolutionary steps in the Giardia genus as it adapted to different hosts and it provides a powerful foundation for mechanistic exploration of host-pathogen interaction in the G. muris – mouse pathosystem.Author summaryThe Giardia genus comprises eukaryotic single-celled parasites that infect many animals. The Giardia intestinalis species complex, which can colonize and cause diarrheal disease in humans and different animal hosts has been extensively explored at the genomic and cell biologic levels. Other Giardia species, such as the mouse parasite Giardia muris, have remained uncharacterized at the genomic level, hampering our understanding of in vivo host-pathogen interactions and the impact of host dependence on the evolution of the Giardia genus. We discovered that the G. muris genome encodes many of the same virulence factors as G. intestinalis. The G. muris genome has undergone genome contraction, potentially in response to a more defined infective niche in the murine host. We describe differences in metabolic and microbiome modulatory gene repertoire, mediated mainly by lateral gene transfer, that could be important for understanding infective success across the Giardia genus. Our findings provide new insights for the use of G. muris as a powerful model for exploring host-pathogen interactions in giardiasis.