Perusal of parasitic nematode ‘omics in the post-genomic era

Stoltzfus, Jonathan D.; Pilgrim, Adeiye; Herbert, De’Broski R.

doi:10.1016/j.molbiopara.2016.11.003

Cited by 13 publications

(7 citation statements)

References 114 publications

(145 reference statements)

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“…In this context, the employment of high-throughput next-generation sequencing (NGS) methods is greatly increasing. In the last decade, such approaches, combined with advances in computational biology and bioinformatics, have accelerated discoveries within basic and biomedical research for many parasitic diseases [ 16 , 17 ].…”

Section: Introductionmentioning

confidence: 99%

Advances in Omic Studies Drive Discoveries in the Biology of Anisakid Nematodes

D’Amelio¹,

Lombardo²,

Pizzarelli³

et al. 2020

Genes

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Advancements in technologies employed in high-throughput next-generation sequencing (NGS) methods are supporting the spread of studies that, combined with advances in computational biology and bioinformatics, have greatly accelerated discoveries within basic and biomedical research for many parasitic diseases. Here, we review the most updated “omic” studies performed on anisakid nematodes, a family of marine parasites that are causative agents of the fish-borne zoonosis known as anisakiasis or anisakidosis. Few deposited data on Anisakis genomes are so far available, and this still hinders the deep and highly accurate characterization of biological aspects of interest, even as several transcriptomic and proteomic studies are becoming available. These have been aimed at discovering and characterizing molecules specific to peculiar developmental parasitic stages or tissues, as well as transcripts with pathogenic potential as toxins and allergens, with a broad relevance for a better understanding of host–pathogen relationships and for the development of reliable diagnostic tools.

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Section: Introductionmentioning

confidence: 99%

Advances in Omic Studies Drive Discoveries in the Biology of Anisakid Nematodes

D’Amelio¹,

Lombardo²,

Pizzarelli³

et al. 2020

Genes

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“…Parasitic nematodes continue to be a major source of mortality and morbidity worldwide, infecting nearly 25% of the global population [1, 2]. The molecules that are released by these parasites, including the excreted/secreted proteins (ESPs), represent the major interface between hosts and parasites, and directly influence the survival and health of the parasites as well as the pathology they cause to the hosts [3, 4]. Despite an abundance of studies addressing mechanistic aspects of host immune response to nematode parasites, there is a distinct paucity of molecular information about most parasitic nematodes, where few secreted molecules have been studied in detail.…”

Section: Introductionmentioning

confidence: 99%

A core set of venom proteins is released by entomopathogenic nematodes in the genus Steinernema

Chang

Serra

et al. 2019

PLoS Pathog

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Parasitic helminths release molecular effectors into their hosts and these effectors can directly damage host tissue and modulate host immunity. Excreted/secreted proteins (ESPs) are one category of parasite molecular effectors that are critical to their success within the host. However, most studies of nematode ESPs rely on in vitro stimulation or culture conditions to collect the ESPs, operating under the assumption that in vitro conditions mimic actual in vivo infection. This assumption is rarely if ever validated. Entomopathogenic nematodes (EPNs) are lethal parasites of insects that produce and release toxins into their insect hosts and are a powerful model parasite system. We compared transcriptional profiles of individual Steinernema feltiae nematodes at different time points of activation under in vitro and in vivo conditions and found that some but not all time points during in vitro parasite activation have similar transcriptional profiles with nematodes from in vivo infections. These findings highlight the importance of experimental validation of ESP collection conditions. Additionally, we found that a suite of genes in the neuropeptide pathway were downregulated as nematodes activated and infection progressed in vivo , suggesting that these genes are involved in host-seeking behavior and are less important during active infection. We then characterized the ESPs of activated S . feltiae infective juveniles (IJs) using mass spectrometry and identified 266 proteins that are released by these nematodes. In comparing these ESPs with those previously identified in activated S . carpocapsae IJs, we identified a core set of 52 proteins that are conserved and present in the ESPs of activated IJs of both species. These core venom proteins include both tissue-damaging and immune-modulating proteins, suggesting that the ESPs of these parasites include both a core set of effectors as well as a specialized set, more adapted to the particular hosts they infect.

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“…Despite the wealth of literature supporting the therapeutic use of helminth ESPs for treating inflammatory disorders, the capacity of a crude parasite-derived supernatant to be developed as a drug is limited. ESP proteomes from many distinct species of helminths have been characterized, and their annotation has been supported by the increasing number of draft genomes [64]. Although a handful of individual proteins with immunoregulatory properties have been identified from ESPs, helminth-secreted proteomes still present a relatively untapped pharmacopeia [65,66].…”

Section: Helminth Therapeutic Moietiesmentioning

confidence: 99%

Harnessing helminth-driven immunoregulation in the search for novel therapeutic modalities

et al. 2020

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Parasitic helminths have coevolved with humans over millennia, intricately refining and developing an array of mechanisms to suppress or skew the host's immune system, thereby promoting their long-term survival. Some helminths, such as hookworms, cause little to no overt pathology when present in modest numbers and may even confer benefits to their human host. To exploit this evolutionary phenomenon, clinical trials of human helminth infection have been established and assessed for safety and efficacy for a range of immune dysfunction diseases and have yielded mixed outcomes. Studies of live helminth therapy in mice and larger animals have convincingly shown that helminths and their excretory/secretory products possess anti-inflammatory drug-like properties and represent an untapped pharmacopeia. These anti-inflammatory moieties include extracellular vesicles, proteins, glycans, post-translational modifications, and various metabolites. Although the concept of helminth-inspired therapies holds promise, it also presents a challenge to the drug development community, which is generally unfamiliar with foreign biologics that do not behave like antibodies. Identification and characterization of helminth molecules and vesicles and the molecular pathways they target in the host present a unique opportunity to develop tailored drugs inspired by nature that are efficacious, safe, and have minimal immunogenicity. Even so, much work remains to mine and assess this out-of-the-box therapeutic modality. Industry-based organizations need to consider long-haul investments aimed at unraveling and exploiting unique and differentiated mechanisms of action as opposed to toe-dipping entries with an eye on rapid and profitable turnarounds.

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Perusal of parasitic nematode ‘omics in the post-genomic era

Cited by 13 publications

References 114 publications

Advances in Omic Studies Drive Discoveries in the Biology of Anisakid Nematodes

Advances in Omic Studies Drive Discoveries in the Biology of Anisakid Nematodes

A core set of venom proteins is released by entomopathogenic nematodes in the genus Steinernema

Harnessing helminth-driven immunoregulation in the search for novel therapeutic modalities

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