Biology subjects

Pearson, M. S.

Publications and source records attributed to Pearson, M. S..

3 recordsLinked to original sources

bioRxiv2020

Schistosoma haematobium extracellular vesicle proteins confer protection in a heterologous model of schistosomiasis

Helminth parasites release extracellular vesicles which interact with the surrounding host tissues, mediating host-parasite communication and other fundamental processes of parasitism. As such, vesicle proteins present attractive targets for the development of novel intervention strategies to control these parasites and the diseases they cause. Herein, we describe the first proteomic analysis by LC-MS/MS of two types of extracellular vesicles (exosome-like, 120k pellet vesicles and microvesicle-like, 15k pellet vesicles) from adult Schistosoma haematobium worms. A total of 57 and 330 proteins were identified in the 120k pellet vesicles and larger 15k pellet vesicles, respectively, and some of the most abundant molecules included homologues of known helminth vaccine and diagnostic candidates such as Sm-TSP2, Sm23, glutathione S-tranferase, saposins and aminopeptidases. Tetraspanins were highly represented in the analysis and found in both vesicle types. Vaccination of mice with recombinant versions of three of these tetraspanins induced protection in a heterologous challenge (S. mansoni) model of infection, resulting in significant reductions (averaged across two independent trials) in liver (47%, 38% and 41%) and intestinal (47%, 45% and 41%) egg burdens. These findings offer insight into the mechanisms by which anti-tetraspanin antibodies confer protection and highlight the potential that extracellular vesicle surface proteins offer as anti-helminth vaccines.

microbiology↗

bioRxiv2019

Novel cholinesterase paralogs of Schistosoma mansoni have perceived roles in cholinergic signaling, glucose scavenging and drug detoxification and are essential for parasite survival

Cholinesterase (ChE) function in schistosomes is essential for orchestration of parasite neurotransmission but has been poorly defined with respect to the molecules responsible. Interrogation of the S. mansoni genome has revealed the presence of three ChE domain-containing genes (Smche)s, which we have shown to encode two functional acetylcholinesterases (AChE)s (Smache1 - smp_154600 and Smache3 - smp_136690) and a butyrylcholinesterase (BChE) (Smbche1 - smp_125350). Antibodies to recombinant forms of each SmChE localized the proteins to the tegument and neuromusculature of adults and schistosomula and developmental expression profiling differed among the three molecules, suggestive of functions extending beyond traditional cholinergic signaling. For the first time in schistosomes, we identified ChE enzymatic activity in fluke excretory/secretory (ES) products and, using proteomic approaches, attributed this activity to the presence of SmAChE1 and SmBChE1. To address the hypothesis that tegumental AChE mediates exogenous glucose scavenging by the parasite, we show that RNAi-mediated knockdown of smache1 and smache3, but not smbche1, significantly reduces glucose uptake by schistosomes. Parasite survival in vitro and in vivo was significantly impaired by silencing of each smche, either individually or in combination, attesting to the essential roles of these molecules. Lastly, in the first characterization study of a BChE from helminths, evidence is provided that SmBChE1 may act as a bio-scavenger of AChE inhibitors as the addition of recombinant SmBChE1 to parasite cultures mitigated the effect of the anti-schistosome AChE inhibitor DDVP (DDVP), whereas smbche1-silenced parasites displayed increased sensitivity to DDVP.\n\nAuthor summaryCholinesterases - aceytlcholinesterases (AChE)s and butyrylcholinesterases (BChE)s - are multi-functional enzymes that play a pivotal role in the nervous system of parasites by regulating neurotransmission through acetylcholine hydrolysis. Herein, we provide a detailed characterization of schistosome cholinesterases using molecular, enzymatic and gene-silencing approaches and show evidence for these molecules having roles in glucose scavenging and drug detoxification, in addition to their neuronal function. Further, we demonstrate the importance of these proteins to parasite development and survival through gene knockdown experiments in laboratory animals, providing evidence for the use of these proteins in the development of novel intervention strategies against schistosomiasis.

molecular biology↗

bioRxiv2018

In-depth proteomic characterization of Schistosoma haematobium: towards the development of new tools for elimination

BackgroundSchistosomiasis is a neglected disease affecting hundreds of millions worldwide. Of the three main species affecting humans, Schistosoma haematobium is the most common, and is the leading cause of urogenital schistosomiasis. S. haematobium infection can cause different urogential clinical complications, particularly in the bladder, and furthermore, this parasite has been strongly linked with squamous cell carcinoma. A comprehensive analysis of the molecular composition of its different proteomes will contribute to developing new tools against this devastating disease.\n\nMethods and FindingsBy combining a comprehensive protein fractionation approach consisting of OFFGEL electrophoresis with high-throughput mass spectrometry, we have performed the first in-depth characterisation of the different discrete proteomes of S. haematobium that are predicted to interact with human host tissues, including the secreted and tegumental proteomes of adult flukes and secreted and soluble egg proteomes. A total of 662, 239, 210 and 138 proteins were found in the adult tegument, adult secreted, soluble egg and secreted egg proteomes, respectively. In addition, we probed these distinct proteomes with urine to assess urinary antibody responses from naturally infected human subjects with different infection intensities, and identified adult fluke secreted and tegument extracts as being the best predictors of infection.\n\nConclusionWe provide a comprehensive dataset of proteins from the adult and egg stages of S. haematobium and highlight their utility as diagnostic markers of infection intensity for the development of novel tools to control this important neglected tropical disease.\n\nAuthor SummarySchistosomiasis is a neglected tropical disease affecting millions of people worldwide. Of the main three species affecting humans, Schistosoma haematobium is the most common, and is the leading cause of urogenital schistosomiasis. This parasite can cause a range of clinical complications associated with bladder pathogenesis, including squamous cell carcinoma as well as genital malignancy in women. Herein, we have performed the first comprehensive characterisation of the proteins implicated in host-parasite interactions (secreted and surface proteins from the adult flukes and secreted and soluble egg proteins) in order to advance our understanding of the parasites biology. Furthermore, we have characterised the different antibody responses in urine from infected human subjects from an endemic area presenting different infection intensities. The data obtained in this study can be used as a first step towards the development of novel tools for the control of urogenital schistosomiasis.

microbiology↗