Stage and tissue expression patterns of Schistosoma mansoni venom allergen-like proteins SmVAL 4, 13, 16 and 24

Abstract Background Schistosoma mansoni venom allergen-like protein (SmVAL) is a gene family composed of 29 members divided into group 1 encoding proteins potentially secreted, and group 2 encoding intracellular components. Some members were found to be upregulated in the transition of germ ball - cercariae - day 3 schistosomula, suggesting that group 1 SmVAL proteins are associated with the invasion of the human host, although their functions are not completely established. Recently, we have described the localization of SmVAL7 (group 1) and SmVAL6 (group 2) transcripts in the oesophageal gland and in the oral and ventral suckers of adult parasites, respectively. The expression patterns of the two genes suggest that SmVAL7 protein plays a role in the blood-feeding process while SmVAL6 is associated with the parasite attachment and movement in the vasculature. In this way, searching for additional secreted SmVAL proteins that could be involved in key processes from skin penetration to the beginning of blood-feeding, we investigated the tissue localization of SmVAL4, 13, 16 and 24 by whole-mount in situ hybridization (WISH). Results We report here the localization of group 1 SmVAL4 and 24 transcripts in the pre-acetabular glands of developing germ balls. Time course experiments of in vitro cultured schistosomula after cercariae transformation demonstrated that SmVAL4 protein is secreted during the first 3 h of in vitro culture, correlating with the emptying of acetabular glands as documented by confocal microscopy. In addition, the localization of SmVAL13 transcripts in adult male anterior oesophageal gland suggests that the respective protein may be involved in the first steps of the blood-feeding process. SmVAL16 was localized close to the neural ganglia and requires further investigation. Conclusions Our findings demonstrate that SmVAL proteins have localizations that place them in strategic positions to be considered as potential vaccine candidates as some members are exposed to interaction with the immune system and may participate in key processes of mammalian invasion and parasitism establishment

Algal-Derived Halogenated Sesquiterpenes from <i>Laurencia dendroidea</i> as Lead Compounds in Schistosomiasis Environmental Control

Schistosomiasis has been controlled for more than 40 years with a single drug, praziquantel, and only one molluscicide, niclosamide, raising concern of the possibility of the emergence of resistant strains. However, the molecular targets for both agents are thus far unknown. Consequently, the search for lead compounds from natural sources has been encouraged due to their diverse structure and function. Our search for natural compounds with potential use in schistosomiasis control led to the identification of an algal species, Laurencia dendroidea, whose extracts demonstrated significant activity toward both Schistosoma mansoni parasites and their intermediate host snails Biomphalaria glabrata. In the present study, three seaweed-derived halogenated sesquiterpenes, (−)-elatol, rogiolol, and obtusol are proposed as potential lead compounds for the development of anthelminthic drugs for the treatment of and pesticides for the environmental control of schistosomiasis. The three compounds were screened for their antischistosomal and molluscicidal activities. The screening revealed that rogiolol exhibits significant activity toward the survival of adult worms, and that all three compounds showed activity against S. mansoni cercariae and B. glabrata embryos. Biomonitored fractioning of L. dendroidea extracts indicated elatol as the most active compound toward cercariae larvae and snail embryos

Schistosoma mansoni venom allergen-like protein 18 (SmVAL18) is a plasminogen-binding protein secreted during the early stages of mammalian-host infection

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2018-04-18T17:13:06Z No. of bitstreams: 1 Fernandes R Schistosoma mansoni venom allergen-like...pdf: 1525994 bytes, checksum: a5b5a8a1de73c2b0ded6e393837bc259 (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2018-04-18T17:23:51Z (GMT) No. of bitstreams: 1 Fernandes R Schistosoma mansoni venom allergen-like...pdf: 1525994 bytes, checksum: a5b5a8a1de73c2b0ded6e393837bc259 (MD5)Made available in DSpace on 2018-04-18T17:23:51Z (GMT). No. of bitstreams: 1 Fernandes R Schistosoma mansoni venom allergen-like...pdf: 1525994 bytes, checksum: a5b5a8a1de73c2b0ded6e393837bc259 (MD5) Previous issue date: 2018Fundação Butantan and Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP – 2012/23124-4 and FAPESP – 2010/18486-9).Instituto Butantan. Laboratorio de Desenvolvimento de Vacinas. São Paulo, SP, Brasil / Universidade de São Paulo. Pós-Graduação Interunidades em Biotecnologia. São Paulo, SP, BrasilInstituto Butantan. Laboratorio de Desenvolvimento de Vacinas. São Paulo, SP, Brasil / Universidade de São Paulo. Pós-Graduação Interunidades em Biotecnologia. São Paulo, SP, BrasilUniversidade de São Paulo. Instituto de Física de São Carlos. São Carlos, SP, BrasilInstituto Butantan. Laboratório de Parasitologia. São Paulo, SP, BrasilInstituto Butantan. Laboratório de Parasitologia. São Paulo, SP, BrasilFundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, BrasilInstituto Butantan. Laboratorio de Desenvolvimento de Vacinas. São Paulo, SP, BrasilInstituto Butantan. Laboratorio de Desenvolvimento de Vacinas. São Paulo, SP, BrasilSchistosomiasis is a neglected tropical disease caused by trematodes of the genus Schistosoma which have a complex life cycle characterized by an asexual multiplication phase in the snail intermediate host and a sexual reproduction phase in the mammalian definitive host. The initial steps of the human host infection involve the secretion of proteins contained in the acetabular glands of cercariae that promote parasite adhesion and proteolysis of the skin layers. Herein, we performed a functional analysis of SmVAL18, identified as one of the three SCP/TAPS proteins constituent of cercarial secretions. We evaluated the SmVAL18 binding to immobilized macromolecules of the extracellular matrix (ECM) and to plasma components. Recombinant protein, expressed in E. coli, was found to maintain an ordered secondary structure typical of the SCP/TAPS domain after purification. Expression of native SmVAL18 protein was verified to be restricted to cercariae and 3-h schistosomula stages; furthermore, the protein was observed in the corresponding secretions, confirming that SmVAL18 is secreted during the first 3 h of in vitro culture. rSmVAL18 was able to interact specifically with plasminogen (PLG) and enhance its conversion into plasmin in the presence of the urokinase-type plasminogen activator (uPA). Protein homology modelling suggested that the PLG-rSmVAL18 interaction was mediated by lysine residues of the protein. This was supported by in vitro data using the lysine analogue, 6-aminocaproic acid (ACA), which abolished the interaction. Finally, our results showed that both cercariae and 3-h schistosomula, as well as their corresponding secretions, exhibited the capacity to bind PLG and enhance its conversion into plasmin in vitro in the same way as observed for the recombinant protein. In conclusion, our findings show that SmVAL18 is a novel PLG-binding protein secreted during the early stages of the mammalian-host infection