Comparative study of excretory–secretory proteins released by Schistosoma mansoni-resistant, susceptible and naïve Biomphalaria glabrata

Abstract

Background Schistosomiasis is a harmful neglected tropical disease caused by infection with Schistosoma spp., such as Schistosoma mansoni. Schistosoma must transition within a molluscan host to survive. Chemical analyses of schistosome-molluscan interactions indicate that host identification involves chemosensation, including naïve host preference. Proteomic technique advances enable sophisticated comparative analyses between infected and naïve snail host proteins. This study aimed to compare resistant, susceptible and naïve Biomphalaria glabrata snail-conditioned water (SCW) to identify potential attractants and deterrents. Methods Behavioural bioassays were performed on S. mansoni miracidia to compare the effects of susceptible, F1 resistant and naïve B. glabrata SCW. The F1 resistant and susceptible B. glabrata SCW excretory–secretory proteins (ESPs) were fractionated using SDS-PAGE, identified with LC-MS/MS and compared to naïve snail ESPs. Protein-protein interaction (PPI) analyses based on published studies (including experiments, co-expression, text-mining and gene fusion) identified S. mansoni and B. glabrata protein interaction. Data are available via ProteomeXchange with identifier PXD015129. Results A total of 291, 410 and 597 ESPs were detected in the susceptible, F1 resistant and naïve SCW, respectively. Less overlap in ESPs was identified between susceptible and naïve snails than F1 resistant and naïve snails. F1 resistant B. glabrata ESPs were predominately associated with anti-pathogen activity and detoxification, such as leukocyte elastase and peroxiredoxin. Susceptible B. glabrata several proteins correlated with immunity and anti-inflammation, such as glutathione S-transferase and zinc metalloproteinase, and S. mansoni sporocyst presence. PPI analyses found that uncharacterised S. mansoni protein Smp_142140.1 potentially interacts with numerous B. glabrata proteins. Conclusions This study identified ESPs released by F1 resistant, susceptible and naïve B. glabrata to explain S. mansoni miracidia interplay. Susceptible B. glabrata ESPs shed light on potential S. mansoni miracidia deterrents. Further targeted research on specific ESPs identified in this study could help inhibit B. glabrata and S. mansoni interactions and stop human schistosomiasis.

Nuclear genome of Bulinus truncatus, an intermediate host of the carcinogenic human blood fluke Schistosoma haematobium

“…Excretory/secretory (ES) proteins are reported to play central roles in snail-schistosome interactions 18 . Within the Bu.…”

“… Protein group Number of proteins predicted for Bu. truncatus Number of ortho-groups Known or proposed roles Pathway associations References Guadeloupe resistance complex (GRC) 11 (15) a 8 Reduces susceptibility to schistosome infection Cellular processes: lysosome, adherens junction, endocytosis; metabolism: glycosaminoglycan degradation 26 Polymorphic transmembrane cluster 2 (PTC2) 8 (11) a 5 Reduces susceptibility to schistosome infection Glycan biosynthesis and metabolism; glycosphingolipid biosynthesis 13 BIRs/IAPs 117 49 Drug response, apoptosis, innate immune responses Apoptosis, ubiquitin mediated proteolysis, NF-kappa beta signalling, 12 , 27 Toll-/IL-1-related proteins 123 49 Reduces susceptibility to schistosome infection, immune response Toll-like receptor signalling, necroptosis, NF-kappa beta signalling and HIF-1 signaling pathway 101 , 102 Cathepsins 21 7 Reduces susceptibility to schistosome infection, excretory/secretory product Transport and catabolism (lysosome, phagosome, autophagy), apoptosis, antigen processing and presentation 18 Chitinases 103 18 Reduces susceptibility to schistosome infection, excretory/secretory product Amino sugar and nucleotide sugar metabolism 18 , 26 Calmodulins 42 28 Stress response, drug susceptibility Immune system: C-type lectin receptor signaling pathway 27 Lectins 101 33 Immune response Immune system; C-type lectin receptor signalling pathway 103 Fibrinogen-related p...…”

“…While there have been major advances in our understanding of the biology and molecular biology of the parasitic trematodes that cause clonorchiasis, opisthorchiasis and schistosomiasis 8 – 11 , this is not the case for the snail intermediate hosts that transmit these diseases. Indeed, the only studies conducted to date 12 , 13 have reported draft genomes for Biomphalaria glabrata – a key intermediate host of the blood fluke Schistosoma mansoni , which causes hepato-intestinal schistosomiasis in humans, to underpin studies of snail-schistosome interactions 12 , 14 – 18 . However, curated genomic resources are lacking for the vast majority of trematode-transmitting snails 19 , which represents a major blind spot for health-related research.…”

Resistance of Biomphalaria alexandrina to Schistosoma mansoni and Bulinus truncatus to Schistosoma haematobium Correlates with Unsaturated Fatty Acid Levels in the Snail Soft Tissue

“…Hemocyte migration and function may be easily impaired by several sporocyst-derived factors, among which antioxidant and immune-modulator molecules, and proteolytic enzymes, notably the metalloproteinase, SmLeish [ 66 – 70 ]. Fortunately, the parasites also fail to develop due to a plethora of intramolluscan immune factors and miracidia deterrents and biochemically unsuitable determinants [ 21 , 26 – 34 , 64 , 71 – 73 ]. Moreover, PUFA level is a target that could be manipulated via diet to prevent snail infection, using PUFA (notably arachidonic acid) synthesizing algae, fungi, and plants [ 74 ].…”

Heat shock protein 70 (Hsp70) in Schistosoma mansoni and its role in decreased adult worm sensitivity to praziquantel

“…The development and reproduction of the parasite are accompanied by downregulation of haemocyte Hsp70 (Zahoor et al ., 2010). A recent proteomic study comparing the excretory secretory products of susceptible and resistant B. glabrata snails detected the presence of Hsp70 cognate 4 in resistant snails only that is involved in the parasite defence or immune protection (Fogarty et al ., 2019). On the other hand, in the human portal blood system, where the parasite experiences an extraordinary increase in biomass and significant morphological alterations, it was found that one constituent of the Hsp complex, Smp_097380.1- heat shock 10 kDa protein 1 was up-regulated.…”