scholarly journals Plant-Based Natural Products for the Discovery and Development of Novel Anthelmintics against Nematodes

Biomolecules ◽  
2020 ◽  
Vol 10 (3) ◽  
pp. 426 ◽  
Author(s):  
Maoxuan Liu ◽  
Sujogya Kumar Panda ◽  
Walter Luyten

Intestinal parasitic nematodes infect approximately two billion people worldwide. In the absence of vaccines for human intestinal nematodes, control of infections currently relies mainly on chemotherapy, but resistance is an increasing problem. Thus, there is an urgent need for the discovery and development of new anthelmintic drugs, especially ones with novel mechanisms of action. Medicinal plants hold great promise as a source of effective treatments, including anthelmintic therapy. They have been used traditionally for centuries and are mostly safe (if not, their toxicity is well-known). However, in most medicinal plants the compounds active against nematodes have not been identified thus far. The free-living nematode C. elegans was demonstrated to be an excellent model system for the discovery of new anthelmintics and for characterizing their mechanism of action or resistance. The compounds discussed in this review are of botanical origin and were published since 2002. Most of them need further studies of their toxicity, mechanisms and structure-activity relationship to assess more fully their potential as drugs.

2016 ◽  
Vol 283 (1835) ◽  
pp. 20160942 ◽  
Author(s):  
Jinshui Zheng ◽  
Donghai Peng ◽  
Ling Chen ◽  
Hualin Liu ◽  
Feng Chen ◽  
...  

Plant-parasitic nematodes were found in 4 of the 12 clades of phylum Nematoda. These nematodes in different clades may have originated independently from their free-living fungivorous ancestors. However, the exact evolutionary process of these parasites is unclear. Here, we sequenced the genome sequence of a migratory plant nematode, Ditylenchus destructor . We performed comparative genomics among the free-living nematode, Caenorhabditis elegans and all the plant nematodes with genome sequences available. We found that, compared with C. elegans , the core developmental control processes underwent heavy reduction, though most signal transduction pathways were conserved. We also found D. destructor contained more homologies of the key genes in the above processes than the other plant nematodes. We suggest that Ditylenchus spp. may be an intermediate evolutionary history stage from free-living nematodes that feed on fungi to obligate plant-parasitic nematodes. Based on the facts that D. destructor can feed on fungi and has a relatively short life cycle, and that it has similar features to both C. elegans and sedentary plant-parasitic nematodes from clade 12, we propose it as a new model to study the biology, biocontrol of plant nematodes and the interaction between nematodes and plants.


Parasitology ◽  
2004 ◽  
Vol 128 (S1) ◽  
pp. S49-S70 ◽  
Author(s):  
J. S. GILLEARD

There is increasing interest in the use of the free-living nematode Caenorhabditis elegans as a tool for parasitic nematode research and there are now a number of compelling examples of its successful application. C. elegans has the potential to become a standard tool for molecular helminthology researchers, just as yeast is routinely used by molecular biologists to study vertebrate biology. However, in order to exploit C. elegans in a meaningful manner, we need a detailed understanding of the extent to which different aspects of C. elegans biology have been conserved with particular groups of parasitic nematodes. This review first considers the current state of knowledge regarding the conservation of genome organisation across the nematode phylum and then discusses some recent evolutionary development studies in free-living nematodes. The aim is to provide some important concepts that are relevant to the extrapolation of information from C. elegans to parasitic nematodes and also to the interpretation of experiments that use C. elegans as a surrogate expression system. In general, examples have been specifically chosen because they highlight the importance of careful experimentation and interpretation of data. Consequently, the focus is on the differences that have been found between nematode species rather than the similarities. Finally, there is a detailed discussion of the current status of C. elegans as a heterologous expression system to study parasite gene function and regulation using successful examples from the literature.


Parasitology ◽  
2017 ◽  
Vol 145 (8) ◽  
pp. 979-987 ◽  
Author(s):  
Gustavo Salinas ◽  
Gastón Risi

AbstractThe free-living nematode Caenorhabditis elegans is the simplest animal model organism to work with. Substantial knowledge and tools have accumulated over 50 years of C. elegans research. The use of C. elegans relating to parasitic nematodes from a basic biology standpoint or an applied perspective has increased in recent years. The wealth of information gained on the model organism, the use of the powerful approaches and technologies that have advanced C. elegans research to parasitic nematodes and the enormous success of the omics fields have contributed to bridge the divide between C. elegans and parasite nematode researchers. We review key fields, such as genomics, drug discovery and genetics, where C. elegans and nematode parasite research have convened. We advocate the use of C. elegans as a model to study helminth metabolism, a neglected area ready to advance. How emerging technologies being used in C. elegans can pave the way for parasitic nematode research is discussed.


Parasitology ◽  
2010 ◽  
Vol 138 (2) ◽  
pp. 237-248 ◽  
Author(s):  
GILLIAN STEPEK ◽  
GILLIAN McCORMACK ◽  
ANDREW J. BIRNIE ◽  
ANTONY P. PAGE

SUMMARYNematodes represent one of the most abundant and species-rich groups of animals on the planet, with parasitic species causing chronic, debilitating infections in both livestock and humans worldwide. The prevalence and success of the nematodes is a direct consequence of the exceptionally protective properties of their cuticle. The synthesis of this cuticle is a complex multi-step process, which is repeated 4 times from hatchling to adult and has been investigated in detail in the free-living nematode, Caenorhabditis elegans. This process is known as moulting and involves numerous enzymes in the synthesis and degradation of the collagenous matrix. The nas-36 and nas-37 genes in C. elegans encode functionally conserved enzymes of the astacin metalloprotease family which, when mutated, result in a phenotype associated with the late-stage moulting defects, namely the inability to remove the preceding cuticle. Extensive genome searches in the gastrointestinal nematode of sheep, Haemonchus contortus, and in the filarial nematode of humans, Brugia malayi, identified NAS-36 but not NAS-37 homologues†. Significantly, the nas-36 gene from B. malayi could successfully complement the moult defects associated with C. elegans nas-36, nas-37 and nas-36/nas-37 double mutants, suggesting a conserved function for NAS-36 between these diverse nematode species. This conservation between species was further indicated when the recombinant enzymes demonstrated a similar range of inhibitable metalloprotease activities.


Parasitology ◽  
2018 ◽  
Vol 146 (3) ◽  
pp. 314-320 ◽  
Author(s):  
Veeren M Chauhan ◽  
David I Pritchard

AbstractCaenorhabditis elegans is a free-living nematode that resides in soil and typically feeds on bacteria. We postulate that haematophagic C. elegans could provide a model to evaluate vaccine responses to intestinal proteins from hematophagous nematode parasites, such as Necator americanus. Human erythrocytes, fluorescently labelled with tetramethylrhodamine succinimidyl ester, demonstrated a stable bright emission and facilitated visualization of feeding events with fluorescent microscopy. C. elegans were observed feeding on erythrocytes and were shown to rupture red blood cells upon capture to release and ingest their contents. In addition, C. elegans survived equally on a diet of erythrocytes. There was no statistically significant difference in survival when compared with a diet of Escherichia coli OP50. The enzymes responsible for the digestion and detoxification of haem and haemoglobin, which are key components of the hookworm vaccine, were found in the C. elegans intestine. These findings support our postulate that free-living nematodes could provide a model for the assessment of neutralizing antibodies to current and future hematophagous parasite vaccine candidates.


2014 ◽  
Vol 60 (1) ◽  
Author(s):  
Romina E. D’Almeida ◽  
María R. Alberto ◽  
Phillip Morgan ◽  
Margaret Sedensky ◽  
María I. Isla

AbstractZuccagnia punctata Cav. (Fabaceae), commonly called jarilla macho or pus-pus, is being used in traditional medicine as an antiseptic, anti-inflammatory and to relieve muscle and bone pain. The aim of this work was to study the anthelmintic effects of three structurally related flavonoids present in aerial parts of Z. punctata Cav. The biological activity of the flavonoids 7-hydroxyflavanone (HF), 3,7-dihydroxyflavone (DHF) and 2´,4´-dihydroxychalcone (DHC) was examined in the free-living nematode Caenorhabditis elegans. Our results showed that among the assayed flavonoids, only DHC showed an anthelmintic effect and alteration of egg hatching and larval development processes in C. elegans. DHC was able to kill 50% of adult nematodes at a concentration of 17 μg/mL. The effect on larval development was observed after 48 h in the presence of 25 and 50 μg/mL DHC, where 33.4 and 73.4% of nematodes remained in the L3 stage or younger. New therapeutic drugs with good efficacy against drug-resistant nematodes are urgently needed. Therefore, DHC, a natural compound present in Z. punctata, is proposed as a potential anthelmintic drug.


Nematology ◽  
2011 ◽  
Vol 13 (5) ◽  
pp. 553-559 ◽  
Author(s):  
Robert McSorley

AbstractFree-living nematodes in soil ecosystems are vital in the decomposition of organic matter and recycling of nutrients. The effects of various types of disturbances on nematode assemblages were examined in several experiments on a single soil: a short-term detrimental disturbance from solarisation, a short-term beneficial disturbance from amendment addition, and a long-term detrimental disturbance from bare ground without plant cover. Comparison of solarised and non-solarised field plots revealed lower numbers of fungivores in solarised plots. As a result, indices involving ratios of fungivores to bacterivores and fungivores to total free-living nematodes were decreased as well. Addition of an amendment increased numbers of bacterivores. This change was also reflected in calculated indices that expressed trophic groups as percentages of the total free-living nematodes. A severely disturbed site with bare ground that was without plant cover for more than 5 years was compared with an adjacent site maintained in grass. No plant-parasitic nematodes were recovered from the bare ground site, which contained lower numbers of nematodes in all trophic groups than the grass site. However, the structure of the free-living nematode assemblages in both sites was similar, as indicated by the proportions of various trophic groups and by ratios of fungivores and bacterivores. The free-living nematode assemblage in a site with a perceived severe long-term disturbance maintained a trophic structure similar to a site with perennial plant cover.


Nematology ◽  
2005 ◽  
Vol 7 (5) ◽  
pp. 761-766 ◽  
Author(s):  
Nancy Lu ◽  
Rekha Balachandar

AbstractCaenorhabditis elegans is a free-living nematode cultured in an axenic medium, the Caenorhabditis elegans Maintenance Medium (CeMM), which contains B-vitamins, salts, amino acids, nucleic acid substituents, growth factors and glucose as an energy source. After initial experiments established that either pantothenate or pantethine would satisfy the vitamin B5 requirement in C. elegans, reproduction in the nematodes was measured in eight equimolar concentrations of calcium pantothenate, pantethine or coenzyme A. The optimal levels for pantothenate were found to be 7.5, 30 and 120 μg ml−1. The optimal levels for pantethine and coenzyme A were found to be 35 μg ml−1 and 100 μg ml−1, respectively. Among the three compounds, coenzyme A (at 100 μg/ml) supported a significantly greater population growth and, perhaps, is a more metabolically active form. Mild toxicity was demonstrated for pantothenate at 480μg ml−1, pantethine at 560 and 140 μg ml−1, and coenzyme A was found to exhibit toxicity at 410 and 1700 μg ml−1. Based on our results, we recommend that in the future the CeMM could be supplemented with pantothenate (7.5 μg ml−1) alone.


2008 ◽  
Vol 99 (6) ◽  
pp. 3136-3143 ◽  
Author(s):  
S. R. Lockery ◽  
K. J. Lawton ◽  
J. C. Doll ◽  
S. Faumont ◽  
S. M. Coulthard ◽  
...  

With a nervous system of only 302 neurons, the free-living nematode Caenorhabditis elegans is a powerful experimental organism for neurobiology. However, the laboratory substrate commonly used in C. elegans research, a planar agarose surface, fails to reflect the complexity of this organism's natural environment, complicates stimulus delivery, and is incompatible with high-resolution optophysiology experiments. Here we present a new class of microfluidic devices for C. elegans neurobiology and behavior: agarose-free, micron-scale chambers and channels that allow the animals to crawl as they would on agarose. One such device mimics a moist soil matrix and facilitates rapid delivery of fluid-borne stimuli. A second device consists of sinusoidal channels that can be used to regulate the waveform and trajectory of crawling worms. Both devices are thin and transparent, rendering them compatible with high-resolution microscope objectives for neuronal imaging and optical recording. Together, the new devices are likely to accelerate studies of the neuronal basis of behavior in C. elegans.


2021 ◽  
Vol 21 (2) ◽  
pp. 134-143
Author(s):  
Nabilah Nabilah ◽  
I Gede Swibawa ◽  
Radix Suharjo ◽  
Yuyun Fitriana

Diversity and abundance of nematodes in guava (Psidium guajava L.) cultivation in Lampung. Crystal guava agroecosystem is inhabited by many species of plant parasitic nematodes. However, information regarding this topic was still limited. This study aimed to understand the species dominancy of nematodes in crystal guava cultivation in Lampung. Sampling was carried out in three locations of guava crystal plantations: Lampung Timur, Lampung Tengah, and Tanggamus. The laboratory analysis was done at the Plant Pest Science Laboratory and Agricultural Biotechnology Laboratory, Universitas Lampung. The study was conducted in December 2019 – July 2020. Nematodes were identified to the level of the genus. The Prominance value (PV) was used to assess the nematodes genus dominancy. The results showed that the nematodes inhabiting the crystal guava agro-ecosystem in Lampung was both plant parasitic and free-living nematodes. The plant parasitic nematodes were identified as Meloidogyne, Aphelenchus, Hemicriconemoides, Tylenchus, Aphelenchoides, and Xiphinema, while free-living nematodes was Rhabditis, Dorylaimine, Dorylaimus, and Mononchus. The dominant plant parasitic nematode was Meloidogyne and the dominant free-living nematode was Rhabditis. The abundance of Meloidogyne /300 mL of soil was 351.47 individuals in Lampung Timur, 124.27 individuals in Lampung Tengah, and 82.18 individuals in Tanggamus. The dominant free-living nematode in the three locations was Rhabditis.


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