Proteomic profiling of serum extracellular vesicles identifies diagnostic markers for echinococcosis

Abstract

Echinococcosis is a parasitic disease caused by the metacestodes of Echinococcus spp. The disease has a long latent period and is largely underdiagnosed, partially because of the lack of effective early diagnostic approaches. Using liquid chromatography-mass spectrometry, we profiled the serum-derived extracellular vesicles (EVs) of E. multilocularis-infected mice and identified three parasite-origin proteins, thioredoxin peroxidase 1 (TPx-1), transitional endoplasmic reticulum ATPase (TER ATPase), and 14-3-3, being continuously released by the parasites into the sera during the infection via EVs. Using ELISA, both TPx-1 and TER ATPase were shown to have a good performance in diagnosis of experimental murine echinococcosis as early as 10 days post infection and of human echinococcosis compared with that of control. Moreover, TER ATPase and TPx-1 were further demonstrated to be suitable for evaluation of the prognosis of patients with treatment. The present study discovers the potential of TER ATPase and TPx-1 as promising diagnostic candidates for echinococcosis.

The proteome of extracellular vesicles of the lung fluke Paragonimus kellicotti produced in vitro and in the lung cyst

“…This protein is involved in endoplasmic reticulum membrane homeostasis and ubiquitination, and it has been detected in EV released from cancer cells 31 – 33 . Moreover, this ATPase was one of the three parasite-derived proteins found in serum EV from Echinococcus multilocularis -infected mice at different times after infection 34 . The authors describe this protein as a biomarker candidate for early diagnosis of echinococcosis.…”

Progresses and challenges in Strongyloides spp. proteomics

“…Such analysis could however be particularly useful in revealing novel facets of the pathological mechanisms associated with human strongyloidiasis, especially when applied in comparative studies. Indeed, this strategy has already been successfully applied to the study of other helminthiases, including schistosomiasis, fasciolosis and echinococcosis, to identify proteins or biological processes altered in the pathological state compared to uninfected controls, during the disease progression or in response to treatment [66][67][68][69][70][71][72][73][74][75][76]. The most commonly investigated samples are plasma/serum and plasma/serumderived EVs (either from animal models or from patients), even though also tissue proteomics has been described [69,70].…”

“…The most commonly investigated samples are plasma/serum and plasma/serumderived EVs (either from animal models or from patients), even though also tissue proteomics has been described [69,70]. Importantly, a number of studies identified parasite proteins within the host's systemic or vesicular proteome, supporting the relevance of host proteomics also in revealing novel diagnostic markers [67,68,71,72,74,75]. Considering strongyloidiasis, many studies have investigated the systemic host response to the infection through the measurement of specific circulating factors, especially cytokines [11,[77][78][79][80][81][82][83].…”

“…The most commonly investigated samples are plasma/serum and plasma/serum-derived EVs (either from animal models or from patients), even though also tissue proteomics has been described [69,70]. Importantly, a number of studies identified parasite proteins within the host's systemic or vesicular proteome, supporting the relevance of host proteomics also in revealing novel diagnostic markers [67,68,71,72,74,75].…”

Characterization and Proteomic Analysis of Plasma EVs Recovered from Healthy and Diseased Dogs with Canine Leishmaniosis

“…In this context, EVs are a resource with great potential [ 2 ], as these small lipidic vesicles of cellular origin are present in all biological fluids and have great stability. In fact, the potential of EVs as a source of disease-relevant biomarkers has been proposed for other parasitic pathogens [ 14 , 15 , 16 , 17 , 18 ]. EVs from Leishmania have been previously characterized [ 19 , 20 ] and parasite-associated proteins were also identified in infected macrophages [ 21 , 22 , 23 ].…”