scholarly journals In silico analyses of neuropeptide-like protein (NLP) profiles in parasitic nematodes

2021 ◽  
Author(s):  
Fiona M McKay ◽  
Ciaran J McCoy ◽  
Nikki J Marks ◽  
Aaron G Maule ◽  
Louise E Atkinson ◽  
...  
Keyword(s):  
Drug Targets ◽  
Anthelmintic Resistance ◽  
Physiological Activity ◽  
Nematode Species ◽  
Nematode Parasite ◽  
Parasitic Nematodes ◽  
Global Food Security ◽  
Nematode Parasites ◽  
Parasite Infections ◽  
Novel Drug

Nematode parasite infections cause disease in humans and animals and threaten global food security by reducing productivity in livestock and crop farming. The escalation of anthelmintic resistance in economically important nematode parasites underscores the need for the identification of novel drug targets in these worms. Nematode neuropeptide signalling is an attractive system for potential chemotherapeutic exploitation, with neuropeptide G-protein coupled receptors (NP-GPCRs) representing the leading target candidates therein. In order to successfully validate NP-GPCRs as targets for parasite control it is necessary to characterise their function and importance to nematode biology. This can be aided through identifying receptor activating ligand(s) in a process known as receptor deorphanisation. Such efforts first require the identification of all neuropeptide ligands within parasites. Here we comb the genomes of nine therapeutically relevant pathogenic nematode species to comprehensively characterise the nematode parasite neuropeptide-like protein (NLP) complements, and details the discovery of several previously unreported, yet conserved, neuropeptides and neuropeptide-encoding genes. We identify the neuropeptides that are most highly conserved in all parasites examined, and characterise their physiological activity on the reproductive musculature of the parasite, Ascaris suum. These data suggest conserved neuropeptide functions in both free living and parasitic nematodes, and support the potential for exploitation of the neuropeptide signalling system as an anthelmintic target.

scholarly journals Phylum-Spanning Neuropeptide GPCR Identification and Prioritization: Shaping Drug Target Discovery Pipelines for Nematode Parasite Control

2021 ◽  
Vol 12 ◽  
Author(s):  
Louise E. Atkinson ◽  
Ciaran J. McCoy ◽  
Bethany A. Crooks ◽  
Fiona M. McKay ◽  
Paul McVeigh ◽  
...  
Keyword(s):  
In Silico ◽  
Drug Target ◽  
Drug Targets ◽  
Parasitic Nematode ◽  
Anthelmintic Resistance ◽  
Life Stage ◽  
Nematode Parasite ◽  
Parasitic Nematodes ◽  
Parasite Control ◽  
Specific Expression

Nematode parasites undermine human health and global food security. The frontline anthelmintic portfolio used to treat parasitic nematodes is threatened by the escalation of anthelmintic resistance, resulting in a demand for new drug targets for parasite control. Nematode neuropeptide signalling pathways represent an attractive source of novel drug targets which currently remain unexploited. The complexity of the nematode neuropeptidergic system challenges the discovery of new targets for parasite control, however recent advances in parasite ‘omics’ offers an opportunity for the in silico identification and prioritization of targets to seed anthelmintic discovery pipelines. In this study we employed Hidden Markov Model-based searches to identify ~1059 Caenorhabditis elegans neuropeptide G-protein coupled receptor (Ce-NP-GPCR) encoding gene homologs in the predicted protein datasets of 10 key parasitic nematodes that span several phylogenetic clades and lifestyles. We show that, whilst parasitic nematodes possess a reduced complement of Ce-NP-GPCRs, several receptors are broadly conserved across nematode species. To prioritize the most appealing parasitic nematode NP-GPCR anthelmintic targets, we developed a novel in silico nematode parasite drug target prioritization pipeline that incorporates pan-phylum NP-GPCR conservation, C. elegans-derived reverse genetics phenotype, and parasite life-stage specific expression datasets. Several NP-GPCRs emerge as the most attractive anthelmintic targets for broad spectrum nematode parasite control. Our analyses have also identified the most appropriate targets for species- and life stage- directed chemotherapies; in this context we have identified several NP-GPCRs with macrofilaricidal potential. These data focus functional validation efforts towards the most appealing NP-GPCR targets and, in addition, the prioritization strategy employed here provides a blueprint for parasitic nematode target selection beyond NP-GPCRs.

scholarly journals Prospects of Using High-Throughput Proteomics to Underpin the Discovery of Animal Host–Nematode Interactions

Pathogens ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 825
Author(s):  
Tao Wang ◽  
Robin Gasser
Keyword(s):  
Mass Spectrometry ◽  
High Throughput ◽  
Anthelmintic Resistance ◽  
Nematode Species ◽  
Economic Losses ◽  
Future Research ◽  
Parasitic Nematodes ◽  
Public Health Burden ◽  
Host Parasite Interactions ◽  
Host Parasite

Parasitic nematodes impose a significant public health burden, and cause major economic losses to agriculture worldwide. Due to the widespread of anthelmintic resistance and lack of effective vaccines for most nematode species, there is an urgent need to discover novel therapeutic and vaccine targets, informed through an understanding of host–parasite interactions. Proteomics, underpinned by genomics, enables the global characterisation proteins expressed in a particular cell type, tissue and organism, and provides a key to insights at the host–parasite interface using advanced high-throughput mass spectrometry-based proteomic technologies. Here, we (i) review current mass-spectrometry-based proteomic methods, with an emphasis on a high-throughput ‘bottom-up’ approach; (ii) summarise recent progress in the proteomics of parasitic nematodes of animals, with a focus on molecules inferred to be involved in host–parasite interactions; and (iii) discuss future research directions that could enhance our knowledge and understanding of the molecular interplay between nematodes and host animals, in order to work toward new, improved methods for the treatment, diagnosis and control of nematodiases.

scholarly journals Molecular Diversity of Nematode Parasites in Afrotropical Reed Frogs (Hyperolius spp.)

Diversity ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 265
Author(s):  
Ulrich Sinsch ◽  
J. Maximilian Dehling ◽  
Patrick Scheid ◽  
Carsten Balczun
Keyword(s):  
Dna Sequences ◽  
Nematode Species ◽  
Sub Saharan Africa ◽  
Parasitic Nematodes ◽  
Marker Genes ◽  
Nematode Parasites ◽  
Diversity Assessment ◽  
Wide Range ◽  
Nematode Diversity ◽  
Sub Saharan

The diversity of nematodes infecting amphibians is understudied in tropical Africa and unknown in Rwanda. Diversity assessment is hampered by the fact that species descriptions refer mostly to morphological features that are unlinked to DNA sequences of marker genes available in public databases. In this paper, we explore the abundance and diversity of parasitic nematodes in reed frogs Hyperolius kivuensis (n = 115), H. parallelus (n = 45) and H. viridiflavus (n = 100) collected in Rwanda. Five nematode species were identified morphologically as Orneoascaris chrysanthemoides, O. schoutedeni, Gendria leberrei, Aplectana chamaeleonis and Rhabdias collaris. Corresponding DNA sequences of 18S and COI genes were determined and subsequently deposited in GenBank. Aplectana chamaeleonis showed the highest prevalence (8.7%), but O. chrysanthemoides the highest mean intensity of infection (6.0) and largest number (24) of individuals in H. kivuensis. To the best of our knowledge, all amphibian hosts are new records for these nematode species, which are known to infect a wide range of amphibian and reptile species. Our findings suggest that nematode diversity is probably lower than previously assumed due to low host specificity. As morphological species identification is often challenging, our data facilitate molecular identification of adult and specifically larval nematodes found in amphibians of Sub-Saharan Africa.

scholarly journals Serine/threonine phosphatases in socioeconomically important parasitic nematodes—Prospects as novel drug targets?

2011 ◽  
Vol 29 (1) ◽  
pp. 28-39 ◽  
Author(s):  
Bronwyn E. Campbell ◽  
Andreas Hofmann ◽  
Adam McCluskey ◽  
Robin B. Gasser
Keyword(s):  
Drug Targets ◽  
Parasitic Nematodes ◽  
Novel Drug ◽  
Novel Drug Targets

scholarly journals Complementary Approaches to Understand Anthelmintic Resistance Using Free-Living and Parasitic Nematodes

2020 ◽  
Author(s):  
Janneke Wit ◽  
Clayton Dilks ◽  
Erik Andersen
Keyword(s):  
Haemonchus Contortus ◽  
Parasitic Nematode ◽  
Anthelmintic Resistance ◽  
Nematode Species ◽  
The Other ◽  
Parasitic Nematodes ◽  
Mechanisms Of Resistance ◽  
Free Living ◽  
Sustained Efficacy ◽  
Modes Of Action

Anthelmintic drugs are the major line of defense against parasitic nematode infections, but the arsenal is limited and resistance threatens sustained efficacy of the available drugs. Discoveries of the modes of action of these drugs and mechanisms of resistance have predominantly come from studies of a related non-parasitic nematode species, Caenorhabditis elegans, and the parasitic nematode Haemonchus contortus. Here, we discuss how our understanding of anthelmintic resistance and modes of action came from the interplay of results from each of these species. We argue that this “cycle of discovery”, where results from one species inform the design of experiments in the other, can use the complementary strengths of both to understand anthelmintic modes of action and mechanisms of resistance.

Host immune status affects maturation time in two nematode species – but not as predicted by a simple life-history model

Parasitology ◽  
2003 ◽  
Vol 127 (5) ◽  
pp. 507-512 ◽  
Author(s):  
M. A. GUINNEE ◽  
A. W. GEMMILL ◽  
B. H. K. CHAN ◽  
M. E. VINEY ◽  
A. F. READ
Keyword(s):  
Immune Responses ◽  
Nematode Species ◽  
Parasitic Nematodes ◽  
Nippostrongylus Brasiliensis ◽  
Short Term ◽  
Maturation Time ◽  
Nematode Parasites ◽  
Nude Rats ◽  
Immune Mediated ◽  
Fitness Benefits

In theory, the age at which maturation occurs in parasitic nematodes is inversely related to pre-maturational mortality rate, and cross-species data on mammalian nematodes are consistent with this prediction. Immunity is a major source of parasite mortality and parasites stand to gain sizeable fitness benefits through short-term adjustments of maturation time in response to variation in immune-mediated mortality. The effects of thymus-dependent immune responses on maturation in the nematode parasites Strongyloides ratti and Nippostrongylus brasiliensis were investigated using congenitally thymus-deficient (nude) rats. As compared with worms in normal rats, reproductive maturity of parasites (presence of eggs in utero) in nude rats occurred later in S. ratti but earlier in N. brasiliensis. Immune-mediated differences in maturation time were not associated with differences in worm length. Thymus-dependent immunity had no effect on pre-maturational mortality. Results are discussed in relation to theoretical expectations and possible explanations for the observed patterns in parasite maturation.

NEMATODE PARASITES OF WATERLEAF (Talinum triangulare) IN OBIO-AKPOR AND IKWERRE LOCAL GOVERNMENT AREAS OF RIVERS STATE, NIGERIA

2021 ◽  
Vol 5 (1) ◽  
pp. 140-150
Author(s):  
Adebowale Adegboyega Tanimola ◽  
A. O. Asimiea ◽  
G. Uwaoma
Keyword(s):  
Local Government ◽  
Sampling Technique ◽  
Nematode Species ◽  
Diversity Indices ◽  
Parasitic Nematodes ◽  
Plant Parasitic Nematodes ◽  
Nematode Parasites ◽  
Rivers State ◽  
Talinum Triangulare ◽  
Plant Parasitic

Waterleaf, Talinum triangulare is cultivated in home gardens and fields to improve nutritional quality for the family and a source of livelihood for farmers. However, the role of T. triangulare is often counteracted by plant-parasitic nematodes (PPNs). Effective management of PPNs will depend on the identification and determination of their population and distribution. A survey was conducted in two Local Government Areas (LGAs), Ikwerre and Obio-Akpor of Rivers State to identify plant-parasitic nematodes associated with waterleaf. Multistage random sampling technique was employed in the collection of 60 bulked soil and root samples across six waterleaf monoculture farming communities. The nematodes were extracted, identified and their population determined using standard procedures. Occurrences, relative importance values (RIV) and diversity indices were determined. Other data were analysed using descriptive statistics and analysis of variance. Six plant-parasitic nematodes genera were encountered in this study, Helicotylenchus, Pratylenchus, Paratylenchus, Meloidogyne, Scutellonema and Tylenchulus. Pratylenchus and Helicotylenchus were the most frequently occurring nematode pest genera with equal relative frequency of occurrence of 38.89%. Pratylenchus species with RIV of 61.34% was the most important nematode pest associated with waterleaf across the six farm communities. The dominance index of 0.71 for the nematode genera showed that some nematode species dominated others. Alakahia farms had the highest population of plant-parasitic nematodes (2,780) across the six farm communities, whereas Omagwa farms had the lowest (250). The study showed that nematode pests are associated with waterleaf and could be contributing to yield losses in this crop

scholarly journals PARASITIC NEMATODE INFECTIONS OF ANURANS FROM A DERIVED SAVANNA BIOTOPE IN EDO STATE, NIGERIA

2021 ◽  
Vol 2 (2) ◽  
pp. 166-182
Author(s):  
H. J. Ozemoka ◽  
M. S. O. Aisien
Keyword(s):  
New Record ◽  
Sampling Method ◽  
Parasitic Nematode ◽  
Nematode Species ◽  
Wet Season ◽  
Nematode Parasites ◽  
Derived Savanna ◽  
Parasite Infections ◽  
Edo State ◽  
Cosmocerca Ornata

As part of a broader study to increase the information of parasite infections of anurans from the savanna biotope, an investigation of the nematode parasites of anurans in Agbede, a location in the derived savanna of Edo State, Nigeria was undertaken from August 2007 to July 2008. Anurans were collected at night using the visual acoustic encounter survey (VAES) sampling method, dissected and examined for nematode infections. A total of 329 anurans belonging to sixteen taxa, were examined, of which 235 were infected with an overall prevalence of 71.43%. Seasonal prevalences were 85.63% for wet season and 52.48% for the dry season (p<0.05). Ten nematode species, namely: Amplicaecum africanum, Cosmocerca ornata, Oswaldocruzia hoeplii, Physaloptera sp., Rhabdias africanus, Rhabdias sp., Camallanus dimitrovi, an unidentified oxyurid nematode, Ophidascaris larva, and an unidentified nematode were recovered from the hosts examined. The most common nematode species was Amplicaecum africanum (31.31%), whereas the least common was an unidentified oxyurid nematode (0.30%).Physaloptera sp. is a new record for the anurans of the derived savanna.

Complementary Approaches to Understand Anthelmintic Resistance Using Free-Living and Parasitic Nematodes

2020 ◽  
Author(s):  
Janneke Wit ◽  
Clayton Dilks ◽  
Erik Andersen
Keyword(s):  
Haemonchus Contortus ◽  
Parasitic Nematode ◽  
Anthelmintic Resistance ◽  
Animal Health ◽  
Nematode Species ◽  
Parasitic Nematodes ◽  
Mechanisms Of Resistance ◽  
Free Living ◽  
Powerful Approach ◽  
Anthelmintic Drugs

Parasitic nematode infections impact human and animal health globally, especially in the developing world. Anthelmintic drugs are the major line of defense against these infections, but the arsenal is limited. Additionally, anthelmintic resistance is widespread in veterinary parasites and an emerging threat in human parasites. Discoveries of the mode of action of these drugs and mechanisms of resistance have predominantly come from studies of a related non-parasitic nematode species, Caenorhabditis elegans, and the parasitic nematode Haemonchus contortus. Here, we discuss recent progress understanding anthelmintic resistance using these two species and how that progress relates to laboratory and field-based studies of veterinary helminths. We present a powerful approach enabled by the strengths of both nematode species to understand mechanisms of resistance and modes of action of anthelmintic drugs.

Molecular diagnosis of parasitic nematodes

Parasitology ◽  
1999 ◽  
Vol 117 (7) ◽  
pp. 87-96 ◽  
Author(s):  
J. B. McKEAND
Keyword(s):  
Developmental Stages ◽  
Nematode Species ◽  
Parasitic Nematodes ◽  
Morphological Identification ◽  
Past Infection ◽  
Essential Requirement ◽  
Prevalence Studies ◽  
Nematode Parasites ◽  
Highly Sensitive ◽  
Immunological Assays

There is an essential requirement for highly sensitive tools that will differentiate nematode parasites of animals and plants to the species level. For studying host range, genetic variation, virulence and resistance, the availability of well defined populations is vital. Many nematode species cannot be identified with certainty using traditional morphological or morphometric techniques. This is particularly the case for the more accessible developmental stages that, depending on the particular group concerned, live as eggs and larvae in the environment or as micro-filariae that circulate in the blood or inhabit the skin. Morphological identification of these stages requires specialized expertise and is extremely time consuming. Immunological assays have their place in nematode identification but they do not discriminate between current and previous infections, an essential requirement in many epidemiological and prevalence studies. In addition to being highly sensitive, DNA-based methods of detection define present over past infection and are not dependent on the parasite stage. Many types of methodology are available for the detection and definition of nematode DNA. This paper reviews these methods citing examples that have been used with success in the laboratory as well as the field.

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