Giardipain-1, a protease secreted by Giardia duodenalis trophozoites, causes junctional, barrier and apoptotic damage in epithelial cell monolayers

Ortega‐Pierres, Guadalupe; Argüello-García, Raúl; Laredo-Cisneros, Marco S.; Fonseca-Liñán, Rocío; Gómez-Mondragón, Misael; Inzunza-Arroyo, Rolando; Flores-Benítez, David; Raya‐Sandino, Arturo; Chávez‐Munguía, Bibiana; Ventura-Gallegos, José Luis; Zentella‐Dehesa, Alejandro; Bermúdez‐Cruz, Rosa María; González‐Mariscal, Lorenza

doi:10.1016/j.ijpara.2018.01.006

Cited by 40 publications

(47 citation statements)

References 73 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…G. intestinalis is not known to possess classical virulence factors, such as enterotoxins, but several genes are important for colonization of the host and thus for pathogenesis. These include genes for motility [10], the adhesive disc for attachment [9], secreted cysteine proteases that can degrade host defensive factors [12, 13], and cysteine-rich surface protein like the VSPs [52] and the HCMPs [49] that undergo antigenic variation. The cytoskeletal protein repertoire in G. muris is very similar to G. intestinalis apart from several fragmented alpha-tubulins (three complete genes with homologues in G. intestinalis and nine incomplete gene fragments).…”

Section: Resultsmentioning

confidence: 99%

“…Proteases are important virulence factors in many pathogens and cysteine-protease activities have been suggested to play a role in Giardia virulence [4, 13]. We identified 81 proteins classified as proteases in the G. muris genome, compared to 96 proteins identified in an identical search in G. intestinalis WB (Table S1e).…”

Section: Resultsmentioning

confidence: 99%

“…Giardiasis is also a problem in domestic animals, and the zoonotic potential of Giardia has been highlighted in recent years [5]. In vitro models of the interaction of G. intestinalis with human cells have helped to unravel clues to how Giardia causes disease [6–8], such as the importance of, the adhesive disc for attachment [9], flagella for motility [10, 11], secreted cysteine proteases for interference with host defenses [12–16], interactions with the intestinal microbiota [6, 17], differentiation into cysts for transmission [4, 18] and interference with nitric oxide (NO) production [19, 20]. Despite this progress it remains uncertain whether these in vitro models are representative of the natural infection, particularly because animal models of G. intestinalis infection have significant limitations.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

The compact genome of Giardia muris reveals important steps in the evolution of intestinal protozoan parasites

Jiménez-González

Einarsson

et al. 2020

Microbial Genomics

View full text Add to dashboard Cite

Diplomonad 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.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The compact genome of Giardia muris reveals important steps in the evolution of intestinal protozoan parasites

Jiménez-González

Einarsson

et al. 2020

Microbial Genomics

View full text Add to dashboard Cite

show abstract

“…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%

“…Proteases are important virulence factors in many pathogens and cysteine-protease 283 activities have been suggested to play a role in Giardia virulence 4,13 . We identified 81 284 proteins classified as proteases in the G. muris genome, compared to 96 proteins 285 identified in an identical search in G. intestinalis WB (Table S1E).…”

Section: Virulence Factors In Giardia 263mentioning

confidence: 99%

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

Jiménez-González

Einarsson

et al. 2019

Preprint

View full text Add to dashboard Cite

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.

show abstract

Giardia intestinalis cystatin is a potent inhibitor of papain, parasite cysteine proteases and, to a lesser extent, human cathepsin B

2019

View full text Add to dashboard Cite

Cystatins are important regulators of papain‐like cysteine proteases. In the protozoan parasite Giardia intestinalis, papain‐like cysteine proteases play an essential role in the parasite's biology and pathogenicity. Here, we characterized a cysteine protease inhibitor of G. intestinalis that belongs to type‐I‐cystatins. The parasite cystatin is shown to be a strong inhibitor of papain (Ki ≈ 0.3 nm) and three parasite cysteine proteases (CP14019, CP16160 and CP16779, Ki ≈ 0.9–5.8 nm), but a weaker inhibitor of human cathepsin B (Ki ≈ 79.9 nm). The protein localizes mainly in the cytoplasm. Together, these data suggest that cystatin of G. intestinalis plays a role in the regulation of cysteine protease activities in the parasite and, possibly, in the interaction with the host.

show abstract

Giardipain-1, a protease secreted by Giardia duodenalis trophozoites, causes junctional, barrier and apoptotic damage in epithelial cell monolayers

Cited by 40 publications

References 73 publications

The compact genome of Giardia muris reveals important steps in the evolution of intestinal protozoan parasites

The compact genome of Giardia muris reveals important steps in the evolution of intestinal protozoan parasites

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

Giardia intestinalis cystatin is a potent inhibitor of papain, parasite cysteine proteases and, to a lesser extent, human cathepsin B

Contact Info

Product

Resources

About