Comparative proteomics of adult Paragonimus kellicotti excretion/secretion products released in vitro or present in the lung cyst nodule

Abstract

Paragonimus kellicotti is a zoonotic lung fluke infection, the agent of North American paragonimiasis, and an excellent model for other Paragonimus infections. The excretory/secretory proteins (ESP) released by parasites and presented at the parasite-host interface are frequently proposed to be useful targets for drugs and/or vaccines In vitro culture conditions may alter ESP compared to those produced in vivo. In order to investigate ESPs produced in vivo we took advantage of the fact that adult P. kellicotti reproduce in the lungs of experimentally infected gerbils in tissue cysts. We performed a mass-spectrometric analysis of adult P. kellicotti soluble somatic protein (SSPs) extracts, excreted/secreted proteins (ESPs) produced by adult worms during in vitro culture, and lung cyst fluid proteins (CFPs) from experimentally infected gerbils. We identified 2,137 P. kellicotti proteins that were present in at least two of three biological replicates and supported by at least two peptides. Among those were 1,914 proteins found in SSP, 947 in ESP and 37 in CFP. In silico analysis predicted that only 141 of the total 2,137 proteins were secreted via classical or non-classical pathways. The most abundant functional categories in SSP were storage and oxidative metabolism. The most abundant categories in ESP were proteins related to metabolism and signal transduction. The 37 parasite-related proteins in CFP belonged to 11 functional categories. The largest groups were proteins with unknown function, cytoskeletal proteins and proteasome machinery. 29 of these 37 proteins were shared among all three sample types. To our knowledge, this is the first study that compares in vitro and in vivo ESP for any Paragonimus species. This study has provided new insights into ESPs of food-borne trematodes that are produced and released in vivo. Proteins released at the host-parasite interface may help the parasite evade host immunity and may represent new targets for novel treatments or diagnostic tests for paragonimiasis.

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

“…We compared the current EV proteomic results with our previous CFP and ESP results obtained with the same methodology 6 . From the 915 P. kellicotti -derived proteins found in the ESP in a previous study (Supplementary Table S2 ), 337 were found in the EV ESP that is 60.8% of the proteins present in the EV ESP (Fig.…”

“…Our studies have focused on Paragonimus kellicotti, the agent of North American paragonimiasis, because metacercariae can be easily collected in the USA, they develop into adult worms in gerbils, and because extensive genome and transcriptome data are available for this species 3 – 5 . In a recent study, we used mass spectrometry to study the proteome of adult stage P. kellicotti, their ESP when cultured in vitro, and ESP found in the lung cyst of infected gerbils (cyst fluid proteins, CFP) 6 . This was a significant step toward identification of potential biomarkers for paragonimiasis, but more work was needed.…”

Comparative proteomics analysis of adult Haemonchus contortus isolates from Ovis ammon

“…Previous reports have shown that the development of proteomics differs significantly in different hosts and isolates (Monteiro et al, 2017;Camargo et al, 2018;Di Maggio et al, 2022;Tasbihi et al, 2020). Although there have been several reports on H. contortus infection in sheep, goats, and other ruminant animals, few studies have reported on DEPs of H. contortus worms in domestic O. ammon.…”

“…In parasitological studies, most proteomic analyses are used to understand the biological characteristics of eggs or adult parasites, explore the protein profiles at different developmental stages, and analyze the protein differences at different stages or at the same stage ( Di Maggio et al, 2022 ; Li et al., 2021 ; Wang et al., 2021 ; Wang et al., 2020 ; Hu et al., 2018 ; Wang et al., 2018 ). There are several research reports on the proteomics of H. contortus and its host animals.…”

Immunoblotting Identification of Diagnostic Antigens of Paragonimus westermani Type 1 for the Detection of Human Pulmonary Paragonimiasis in North East India

“…Identification of Paragonimus -species-derived proteins has been possible due to advancements in proteomics, and such studies have provided valuable insights into the biology of parasites and the identification of drug targets. Moreover, proteomics-based studies on diverse parasite antigenic preparations has facilitated unveiling s repertoire of antigens involved in host–parasite interactions [ 31 , 55 ]. A recent study explored the proteome of extracellular vesicles in excretory–secretory products released by P. kellicotti adult worms, providing new insights into the biology of host–parasite interactions and its potential implications in the development of novel diagnostic methods [ 56 ].…”