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Expression and phylogenetic analysis of DNase II–like proteins from Trichuris species. (a) Normalized transcript levels of the 18 genes encoding DNase II domain–containing proteins in T. muris, comparing the parasite anterior region with the posterior regions of adult female and male parasites. Indication of significant transcriptional upregulation in a particular pairwise comparison (Up) refers to FDR % 0.01 and FDR > 1 × 10−5 when denoted by one asterisk and to FDR % 1 × 10−5 when denoted by two asterisks. For a full version of this figure, see Supplementary b. (b) A maximum-likelihood phylogeny of DNase II protein domains (IPR004947) shows the relationships between the DNase II domains of proteins from Trichuris species, T. spiralis, other nematodes, insects and other invertebrates, and vertebrates. See Supplementary for a fully annotated version of this tree. The circled numbers highlight individual sequences of particular interest: (1) TMUE_s0085001500 1–358 (T. muris), TTRE_0000372701 1–317 (T. trichiura) and E5SXW8_TRISP 8–361 (UniProt E5SXW8); (2) TMUE_s0015002900 1–191 and TTRE_0000937801 31–255; and (3) E5S4S7_TRISP 14–306 (UniProt E5S4S7).
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Whipworms are common soil-transmitted helminths that cause debilitating chronic infections in man. These nematodes are only distantly related to Caenorhabditis elegans and have evolved to occupy an unusual niche, tunneling through epithelial cells of the large intestine. We report here the whole-genome sequences of the human-infective Trichuris tri...
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Background: Trichuriasis is an important soil-transmitted helminth infection caused by Trichuris trichiura. About one-tenth of the world population may be infected. Incidentally, T. vulpis or dog whipworm has been reported to infect humans based on the egg size. However, an overlapping egg dimension occurs between T. trichiura and T. vulpis leading...
We examined human stool samples from Liberia for soil-transmitted helminth ova by Kato-Katz smear and by quantitative PCR. Twenty-five samples were positive for Trichuris trichiura by smear but negative by quantitative PCR. Reexamination of samples showed that they contained Capillaria eggs that resemble T. trichiura in Kato-Katz smears.
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... In order to better understand host-pathogen interactions and to drive novel therapeutic development, experimental work in laboratory mouse models has been employed for several decades. A particularly useful helminth model species is T. muris, a natural parasite of M. musculus, which has high genome conservation with T. trichiura [21,22]. Laboratory studies employ largely single dose infections, often classified as either high dose (>100 eggs) or low dose (<40 eggs), in highly controlled environments. ...
Laboratory model organisms have provided a window into how the immune system functions. An increasing body of evidence, however, suggests that the immune responses of naive laboratory animals may differ substantially to those of their wild counterparts. Past exposure, environmental challenges and physiological condition may all impact on immune responsiveness. Chronic infections of soil-transmitted helminths, which we define as establishment of adult, fecund worms, impose significant health burdens on humans, livestock and wildlife, with limited treatment success. In laboratory mice, Th1 versus Th2 immune polarisation is the major determinant of helminth infection outcome. Here we compared antigen-specific immune responses to the soil-transmitted whipworm Trichuris muris between controlled laboratory and wild free-ranging populations of house mice ( Mus musculus domesticus ). Wild mice harbouring chronic, low-level infections produced lower levels of cytokines in response to Trichuris antigen than laboratory-housed C57BL/6 mice. Wild mouse effector/memory CD4+ T cell phenotype reflected the antigen-specific cytokine response across the Th1/Th2 spectrum. Increasing worm burden was associated with body condition loss. However, local Trichuris -specific Th1/Th2 balance was positively associated with worm burden only in older wild mice. Thus, although the fundamental relationships between the CD4+ T helper cell response and resistance to T . muris infection are similar in both laboratory and wild M . m . domesticus , there are quantitative differences and age-specific effects that are analogous to human immune responses. These context-dependent immune responses demonstrate the fundamental importance of understanding the differences between model and natural systems for translating mechanistic models to ‘real world’ immune function.
... Initially, we identified 2823 one-to-one orthologs between T. muris and C. elegans using the BioMart tool based on the annotated genome of T. muris stored in WormBase Parasite [20][21][22] . Following the homology search, we used WormJam as the first reference model to build a draft model for T. muris as WormJam 18 is a consensus metabolic model of previously published C. elegans models. ...
Genome-scale metabolic models are widely used to enhance our understanding of metabolic features of organisms, host-pathogen interactions and to identify therapeutics for diseases. Here we present iTMU798, the genome-scale metabolic model of the mouse whipworm Trichuris muris. The model demonstrates the metabolic features of T. muris and allows the prediction of metabolic steps essential for its survival. Specifically, that Thioredoxin Reductase (TrxR) enzyme is essential, a prediction we validate in vitro with the drug auranofin. Furthermore, our observation that the T. muris genome lacks gsr-1 encoding Glutathione Reductase (GR) but has GR activity that can be inhibited by auranofin indicates a mechanism for the reduction of glutathione by the TrxR enzyme in T. muris. In addition, iTMU798 predicts seven essential amino acids that cannot be synthesised by T. muris, a prediction we validate for the amino acid tryptophan. Overall, iTMU798 is as a powerful tool to study not only the T. muris metabolism but also other Trichuris spp. in understanding host parasite interactions and the rationale design of new intervention strategies.
... For this purpose, the proteome of Trichuris trichiura was screened using an in-silico approach. In 2014, Genome sequencing of Trichuris trichiura reveals genomic size of 75.2 Mb that contains 9650 genes and same number of proteins, with 42.2% GC content, 4439 contig, 4156 scaffolds (70602-N50 and 265-L50 scaffolds) (Foth et al, 2014). ...
Trichuris trichiura is a human parasite belonging to the nematode phylum. It has a genome of 75.2 Mb size that contains more than 9500 genes. Many of these are still uncharacterized proteins. Here, we have tried to annotate a protein bearing Uniprot accession id A0A077Z4I5 using various in silico tools. The amino acid sequence of this protein was subjected to various softwares which demonstrated it to be a Cysteine-knot protein. The motif search revealed the presence of this highly conserved domain, which is believed to be responsible for host parasite interaction and evasion of host immune system by the parasitic nematode. The report of this protein in human parasite T. trichiura is significant as it has not homolog in humans and can be a valid drug target. (2023) Functional and structural annotation of an uncharacterized protein A0A077Z4I5 from Trichuris trichiura.
... There are still many aspects of the biology of the Trichuris parasite that remain undefined [19]. Trichuris muris is an established murine laboratory model for human trichuriasis and shares with Trichuris trichiura many aspects of its biology including the specialized niche within the host [20,21]. ...
Psammomys obesus is a terrestrial rodent's species of gerbil subfamily belong to Muridae. Zoonotic diseases associated with rodents; pose a significant threat to human health and animals. Mouse whip-worm Trichuris muris has been used as a tractable model of human trichuriasis. Zoonotic cestode Rail-lietina sp. causes public health problem when moving from wild habitats to those inhabited by humans. Endoparasitic agents, which can be very serious in human and livestock health, are mostly homed by wild rodents. The current study investigates intestinal helminth infestation of Psammomys obesus. Thirtyseven adult rats were captured from saline marsh areas of North Coast, Egypt. Rats were examined for intestinal parasite with morphological and pathological features. Thirty-three rats were found infected with: Trichuris muris, 16 (48.48, %); Rail-lietina trapezoides, 4 (12.12, %); mixed infection of Trichuris muris and Raillietina trapezoides, 5(15.15%). Gross examination of both small and large intestines revealed intestinal blockage and diarrhea. Histopathological changes of the intestine showed degeneration of the intestinal mucosa; and atrophy of the villi and intestinal glands. Different parts of worms observed in the lumen of colon mu-cosa and at the tip of villi results in discontinuity of the muscularis mucosa and necrotic lesions on the mucosa. Also, necrotic colitis and enteritis were observed. Two types of anemia were confirmed by he-matological analysis. Moreover, two types of eggs were noticed. The helminths infecting Psammomyes obesus were morphologically identified with their pathological effects. Further studies are needed to assess transmitted zoonotic parasitic diseases impact public health in Egypt.
... T. muris is similar to Trichuris trichura (T. trichura) in its biology, so it is used as a laboratory model for trichuriasis in humans in pharmacological, immunological, and genetic research (Feliu et al., 2000;Foth et al., 2014;Aravindhan and Anand, 2017). ...
Trichuridae family has a genetic and morphological variability between species affecting rodents, but it is considerably hard to morphologically diagnose species within the genus of Trichuris and the individuals of these species are identified according to their host, as it is known that Trichuris spp. is strictly host-specific. However, some species lack host specificity. So, it is necessary to use molecular data in order to well identify the Trichuris spp. in Egyptian rodents. The host examined in the current research is Psammomys obesus and the molecularly identified species from its cecum is Trichuris arvicolae. In addition, Trichuris arvicolae was subjected to in vitro treatment with Androctonus crassicauda Crude Venom as a model of natural alternative treatment for gastrointestinal nematodes that increasingly develop anthelmintic drug resistance. The changes in Trichuris arvicolae were monitored using scanning electron microscopy, Androctonus crassicauda Crude Venom made a significant ultrastructural surface changes in Trichuris arvicolae, including marked cuticular sloughing, disintegrated bacillary glands, bursting of vulva and edema of anal region. This study was done for closer identification of Trichuris spp. infecting rodents in Egypt and evaluating the efficacy of Androctonus crassicauda Crude Venom in vitro.
... The naturally occurring infection of Trichuris muris in mice models immune responses to T. trichiuria as the two species have similarities in morphology and genome, occupying the same intestinal niche and sharing antigenic cross-reactivity 6,7 . Multiple factors play a role in determining the immune response to T. muris including infection dose 8 , but the balance of the Th1/Th2 CD4 + T-cell immune response is crucial in determining the outcome of infection 9 . ...
Gastrointestinal nematode infections cause morbidity and socio-economic loss in the most deprived communities. The shift in context of obesity has led to spatial overlap with endemic gastrointestinal nematode regions resulting in the emergence of a novel comorbidity. Despite this, the impact of high fat diet (HFD) on immune-regulated protection against gastrointestinal infections remains largely unknown. We employed the murine model of nematode infection, Trichuris muris, to investigate the effect of a HFD on the immune response against chronic infection. Surprisingly, diet induced obesity drove parasite expulsion in both single and repeated trickle low doses of T. muris eggs. Mechanistically, a HFD increased expression of the ST2 receptor on CD4+ T-cells priming an enhanced Th2 cytokine production following IL-33 stimulation ex vivo. Despite IL-33-/- mice demonstrating that IL-33 is not critical for host protective immunity to T. muris under a conventional diet, HFD fed T-cell deplete mice adoptively transferred with ST2-/- CD4 T-cells were unable to expel a T. muris infection unlike those transferred with ST2 sufficient cells. Collectively, this study demonstrates a HFD primes CD4+ T-cells to utilise the IL-33-ST2 axis in a novel induction of Type 2 immunity, providing insights into the emerging comorbidities of obesity and nematode infection.
... There are over 70 species within the Trichuris genus, each with a different host, including T. trichiura (humans), T. suis (pigs), and T. muris (mouse). Genome and transcriptome analysis of these 3 species was completed in 2014 [2,3]. T. trichiura is the causative agent of human trichuriasis, a neglected tropical disease that affects 477 million people worldwide, causing impaired growth and physical development of children, and gastrointestinal symptoms including diarrhoea, abdominal pain, and rectal prolapse in individuals with heavy worm burdens [1,4]. ...
... There is also a high rate of posttreatment reinfection, emphasising the need for prophylactic vaccines against these parasites [6][7][8]. Progress towards vaccines to protect against whipworm infections has been hindered by a lack of known protective antigens and limited information on the biology of these parasites, despite decades of research involving the closely related, naturally occurring mouse whipworm, T. muris [2,9,10]. ...
... T. muris E/S contains at least 13 WAP proteins and 10 CAP proteins (listed in Tables 1 and 2, respectively) [13,18]. It is our belief that these proteins may warrant further study as vaccine candidates for Trichuris species, given the large number of family members encoded within the genomes of T. muris, T. trichiura, and T. suis (25,20,and 10 WAP and 34,19, and 14 CAP proteins, respectively) (WormBase ParaSite) [19], as well as their possible roles in host-parasite interactions and immunomodulatory properties [2,[20][21][22][23][24][25]. ...
Trichuris trichiura and T . suis are gastrointestinal dwelling roundworms that infect humans and pigs, respectively. Heavy infections cause gastrointestinal symptoms and impaired growth and development. Vaccination has the potential to reduce the disease burden of whipworm infection; however, there are currently no commercially available vaccines against these parasites and very few against other gastrointestinal-dwelling nematodes of medical and agricultural importance. The naturally occurring mouse whipworm, T . muris , has been used for decades to model human trichuriasis, and the immunogenic potential of the excretory/secretory material (E/S, which can be collected following ex vivo culture of worms) has been studied in the context of vaccine candidate identification. Despite this, researchers are yet to progress an effective vaccine candidate to clinical trials. The T . muris , T . trichiura , and T . suis genomes each encode between 10 and 27 whey acidic protein (WAP) domain-containing proteins and 15 to 34 cysteine-rich secretory protein/antigen 5/pathogenesis related-1 (CAP) family members. WAP and CAP proteins have been postulated to play key roles in host–parasite interactions and may possess immunomodulatory functions. In addition, both protein families have been explored in the context of helminth vaccines. Here, we use phylogenetic and functional analysis to investigate the evolutionary relationship between WAP and CAP proteins encoded by T . muris , T . trichiura , and T . suis . We highlight several WAP and CAP proteins that warrant further study to understand their biological function and as possible vaccine candidates against T . trichiura and/or T . suis , based on the close evolutionary relationship with WAP or CAP proteins identified within T . muris E/S products.
... Case studies show other helminths, including Enterobius vermicularis (i.e. pinworm), have also been mistaken for IBD (Rajamanickam et al. 2009, Johansson et al. 2013, Al-Saffar et al. 2015, and similar immune responses observed in Trichuris trichiura infection (Foth et al. 2014, Briggs et al. 2016. Though certain parasites appear to induce colitis-like symptoms, helminth therapy is in fact hypothesized to influence immunoregulatory actions in IBD, and has already been tested in IBD patients (Geremia et al. 2014). ...
Indians who migrate to westernized countries such as Canada, the United States (US), and the United Kingdom (UK) are at an increased risk of developing inflammatory bowel disease (IBD). While the underlying etiology of IBD remains unclear, a gut microbiome that is no longer symbiotic with its host is a major player. Increasing IBD incidence in Indian immigrants may be due to the adoption of western practices that result in loss of tolerance of a symbiotic community in the gut and its underlying immune responses. However, little is known about the microbial changes in the Indian gut, including shifts in the microbiome when they migrate to westernized countries. In this Current Opinion, we discuss what is known about the Indian gut microbiome and how living in a westernized environment may be impeding what was once a symbiotic relationship with their gut microbiome and intestinal mucosae, which may be the driving factor in their increased risk of IBD.
... T. muris, T. trichiura and T. suis show similarities at the genomic and transcriptomic levels: each species has close to 10,000 genes, and roughly half of these are oneto-one orthologues [4,5]. Most of our knowledge on the immune response to whipworm infection comes from studying T. muris infection in mice (reviewed in [6,7]), and T. muris excretory/secretory products (E/S) have provided insight into potential bioreactive molecules, which may have therapeutic potential as vaccine candidates or immunomodulators in the context of allergic and inflammatory diseases. ...
... These SCFAs have been shown to have anti-inflammatory or immunomodulatory activity in multiple models. However, the genome of T. muris indicates that the parasite has the capability to produce acetate and formate but not proprionate, butyrate, isobutyrate, valerate, isovalerate or 2-methylbutanoate [4] (Omer Bay, personal communication), suggesting that they may be derived from bacterial species within T. muris microbiota (which is known to be distinct from the host microbiota) [9,36]. The dominant saturated fatty acid within T. muris E/S is stearic acid which, together with palmitic acid, docosahexaenoic acid, lauric acid and oleic acid, has anti-inflammatory functions, although the functional relevance of these fatty acids within T. muris E/S is yet to be fully understood [35]. ...
... The major T. muris E/S protein, p43, appears to be secreted from the longitudinal muscle layer below the cuticle of the parasite [18]; although whether other E/S proteins are secreted from this site remains to be determined. Foth et al. [4] identified a subset of genes including serine proteases and protease inhibitors with anterior end-specific expression in T. muris and T. trichiura, however the precise location from which these proteins are released remains to be determined; it is possible that they are secreted through pores routed in the bacillary band, a structure unique to Trichurid parasites, however they could also enter the digestive tract via the oesophagus and be released into the external environment of the host via the anus [4]. It is interesting to note that the excretory glands of other parasitic and free-living nematodes are located towards the anterior region and release of E/S from the gastrointestinal tract has also been reported [38,39]. ...
Whipworm (Trichuris) is a genus of roundworms that causes gastrointestinal infections in humans and animals. Of particular interest are T. trichiura, the causative agent of human trichuriasis, a neglected tropical disease that affects 477 million people worldwide, and T. suis, the pig whipworm species, responsible for growth stunting and economic losses within the agricultural industry. The naturally occurring mouse whipworm, T. muris, has been used for decades as a model for trichuriasis, yielding knowledge on the biology of these parasites and the host response to infection. Ex vivo culture of T. muris (and to some extent, T. suis) has provided insight into the composition of the excretory/secretory (E/S) products released by worms, which include a myriad of proteins, RNAs, lipids, glycans, metabolites and extracellular vesicles. T. muris E/S has formed the basis of the search for whipworm vaccine candidates, while the immunomodulatory potential of T. suis and T. muris secretions has been investigated with the aim of improving our understanding of how these parasites modulate host immunity, as well as identifying immunomodulatory candidates with therapeutic potential in the context of inflammatory diseases. This article will review the various components found within Trichuris E/S, their potential as vaccine candidates and their immunomodulatory properties.
Graphical Abstract
... Mapping was performed using BWA-MEM 58 (version 0.7.17-r1188) to an unpublished but significantly improved reference genome of T. trichiura (available here: https://github.com/stephenrdoyle/ancient_trichuris/tree/master/02_data). Originally described by Foth et al. 59 59,60 and are designated by the following prefixes in the reference assembly: Trichuris_trichiura_1 (LG1 [X]; X-chromosome), Trichuris_trichiura_2 (LG2; autosome), and Trichuris_trichiura_3 (LG3; autosome). Scaffolds unassigned to linkage groups have the prefix Trichuris_trichiura_00. ...
... Mapping was performed using BWA-MEM 58 (version 0.7.17-r1188) to an unpublished but significantly improved reference genome of T. trichiura (available here: https://github.com/stephenrdoyle/ancient_trichuris/tree/master/02_data). Originally described by Foth et al. 59 59,60 and are designated by the following prefixes in the reference assembly: Trichuris_trichiura_1 (LG1 [X]; X-chromosome), Trichuris_trichiura_2 (LG2; autosome), and Trichuris_trichiura_3 (LG3; autosome). Scaffolds unassigned to linkage groups have the prefix Trichuris_trichiura_00. ...
The neglected tropical disease trichuriasis is caused by the whipworm Trichuris trichiura,a soil-transmitted helminth that has infected humans for millennia. Today, T. trichiura infects as many as 500 million people, predominantly in communities with poor sanitary infrastructure enabling sustained faecal-oral transmission. Using whole-genome sequencing of geographically distributed worms collected from human and other primate hosts, together with ancient samples preserved in archaeologically-defined latrines and deposits dated up to one thousand years old, we present the first population genomics study of T. trichiura.We describe the continent-scale genetic structure between whipworms infecting humans and baboons relative to those infecting other primates. Admixture and population demographic analyses support a stepwise distribution of genetic variation that is highest in Uganda, consistent with an African origin and subsequent translocation with human migration. Finally, genome-wide analyses between human samples and between human and non-human primate samples reveal local regions of genetic differentiation between geographically distinct populations. These data provide insight into zoonotic reservoirs of human-infective T. trichiura and will support future efforts toward the implementation of genomic epidemiology of this globally important helminth.
