A proteomic comparison of excretion/secretion products in Fasciola hepatica newly excysted juveniles (NEJ) derived from Lymnaea viatrix or Pseudosuccinea columella

Maggio, Lucía Sánchez Di; Tirloni, Lucas; Pinto, Antônio Frederico Michel; Diedrich, Jolene K.; Carmona, Carlos; Berasain, Patrícia; Vaz, Itabajara da Silva

doi:10.1016/j.exppara.2019.04.004

Cited by 10 publications

(8 citation statements)

References 87 publications

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“…The observed stage-specific overexpression of these types of proteins within the juvenile stages of the parasite is directly in line with their migratory and immune-evasion requirements. Interestingly, differences in abundance among proteins belonging to both antioxidant and proteolysis-related pathways have recently been found between secretions of FhNEJ from two different intermediate host species, suggesting that snail hosts influence the proteomic profile of FhNEJ [91].…”

Section: Trends Trends In In Parasitology Parasitologymentioning

confidence: 99%

Insights into Fasciola hepatica Juveniles: Crossing the Fasciolosis Rubicon

González‐Miguel

Becerro-Recio

Siles‐Lucas

2021

Trends in Parasitology

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Section: Trends Trends In In Parasitology Parasitologymentioning

confidence: 99%

Insights into Fasciola hepatica Juveniles: Crossing the Fasciolosis Rubicon

González‐Miguel

Becerro-Recio

Siles‐Lucas

2021

Trends in Parasitology

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“…Recently, much research has focused on the NEJ stage and its means of invasion, since it is this stage that initiates infection and leads to the more damaging later developmental stages. Proteomic and transcriptomic studies have revealed the identity of several peptidases that the NEJ secrete to facilitate infection by breaking down the molecules, cells and tissues of the intestinal wall [ 5 , 9 , 10 , 11 ]. These peptidases include four papain-like cysteine peptides, three F. hepatica cathepsins B (FhCBs), termed FhCB1, FhCB2 and FhCB3 [ 9 , 12 , 13 , 14 , 15 ], and a cathepsin L, termed FhCL3 [ 9 , 16 , 17 ].…”

Section: Introductionmentioning

confidence: 99%

The Zoonotic Helminth Parasite Fasciola hepatica: Virulence-Associated Cathepsin B and Cathepsin L Cysteine Peptidases Secreted by Infective Newly Excysted Juveniles (NEJ)

Barbour

Cwiklinski

Lalor

et al. 2021

Animals

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Fasciolosis caused by Fasciola hepatica is a major global disease of livestock and an important neglected helminthiasis of humans. Infection arises when encysted metacercariae are ingested by the mammalian host. Within the intestine, the parasite excysts as a newly excysted juvenile (NEJ) that penetrates the intestinal wall and migrates to the liver. NEJ excystment and tissue penetration are facilitated by the secretion of cysteine peptidases, namely, cathepsin B1 (FhCB1), cathepsin B2 (FhCB2), cathepsin B3 (FhCB3) and cathepsin L3 (FhCL3). While our knowledge of these peptidases is growing, we have yet to understand why multiple enzymes are required for parasite invasion. Here, we produced functional recombinant forms of these four peptidases and compared their physio-biochemical characteristics. Our studies show great variation of their pH optima for activity, substrate specificity and inhibitory profile. Carboxy-dipeptidase activity was exhibited exclusively by FhCB1. Our studies suggest that, combined, these peptidases create a powerful hydrolytic cocktail capable of digesting the various host tissues, cells and macromolecules. Although we found several inhibitors of these enzymes, they did not show potent inhibition of metacercarial excystment or NEJ viability in vitro. However, this does not exclude these peptidases as targets for future drug or vaccine development.

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“…Among nematodes, the active and continuous shedding of surface proteins is one source of ESP. ESP have been characterized from a variety of helminths, including from their different developmental stages ( Hewitson et al., 2008 ; Liu et al., 2009 ; Geary et al., 2012 ; Sotillo et al., 2014 ; Morante et al., 2017 ; Di Maggio et al., 2019 ). Blood dwelling parasitic helminths and their interference with the mammalian hosts are of particular interest ( Simón et al., 2007 ; Mebius et al., 2013 ): they disrupt blood flow, while interfering with the host’s coagulation in the right balance to neither induce or suppress blood clotting nor bleeding.…”

Section: Introductionmentioning

confidence: 99%

The Angiostrongylus vasorum Excretory/Secretory and Surface Proteome Contains Putative Modulators of the Host Coagulation

Gillis-Germitsch

Kockmann

Asmis

et al. 2021

Front. Cell. Infect. Microbiol.

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Angiostrongylus vasorum is a cardiopulmonary nematode of canids and is, among others, associated with bleeding disorders in dogs. The pathogenesis of such coagulopathies remains unclear. A deep proteomic characterization of sex specific A. vasorum excretory/secretory proteins (ESP) and of cuticular surface proteins was performed, and the effect of ESP on host coagulation and fibrinolysis was evaluated in vitro. Proteins were quantified by liquid chromatography coupled to mass spectrometry and functionally characterized through gene ontology and pathway enrichment analysis. In total, 1069 ESP (944 from female and 959 from male specimens) and 1195 surface proteins (705 and 1135, respectively) were identified. Among these were putative modulators of host coagulation, e.g., von Willebrand factor type D domain protein orthologues as well as several proteases, including serine type proteases, protease inhibitors and proteasome subunits. The effect of ESP on dog coagulation and fibrinolysis was evaluated on canine endothelial cells and by rotational thromboelastometry (ROTEM). After stimulation with ESP, tissue factor and serpin E1 transcript expression increased. ROTEM revealed minimal interaction of ESP with dog blood and ESP did not influence the onset of fibrinolysis, leading to the conclusion that Angiostrongylus vasorum ESP and surface proteins are not solely responsible for bleeding in dogs and that the interaction with the host’s vascular hemostasis is limited. It is likely that coagulopathies in A. vasorum infected dogs are the result of a multifactorial response of the host to this parasitic infection.

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A proteomic comparison of excretion/secretion products in Fasciola hepatica newly excysted juveniles (NEJ) derived from Lymnaea viatrix or Pseudosuccinea columella

Cited by 10 publications

References 87 publications

Insights into Fasciola hepatica Juveniles: Crossing the Fasciolosis Rubicon

Insights into Fasciola hepatica Juveniles: Crossing the Fasciolosis Rubicon

The Zoonotic Helminth Parasite Fasciola hepatica: Virulence-Associated Cathepsin B and Cathepsin L Cysteine Peptidases Secreted by Infective Newly Excysted Juveniles (NEJ)

The Angiostrongylus vasorum Excretory/Secretory and Surface Proteome Contains Putative Modulators of the Host Coagulation

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