scholarly journals A Zinc Metalloprotease nas-33 Is Required for Molting and Survival in Parasitic Nematode Haemonchus contortus

Author(s):  
Yan Huang ◽  
Jie Wu ◽  
Xueqiu Chen ◽  
Danni Tong ◽  
Jingru Zhou ◽  
...  

Molting is of great importance for the survival and development of nematodes. Nematode astacins (NAS), a large family of zinc metalloproteases, have been proposed as novel anthelmintic targets due to their multiple roles in biological processes of parasitic nematodes. In this study, we report a well conserved nas-33 gene in nematodes of clade V and elucidate how this gene is involved in the molting process of the free-living nematode Caenorhabditis elegans and the parasitic nematode Haemonchus contortus. A predominant transcription of nas-33 is detected in the larval stages of these worms, particularly in the molting process. Knockdown of this gene results in marked molecular changes of genes involved in cuticle synthesis and ecdysis, compromised shedding of the old cuticle, and reduced worm viability in H. contortus. The crucial role of nas-33 in molting is closely associated with a G protein beta subunit (GPB-1). Suppression of both nas-33 and gpb-1 blocks shedding of the old cuticle, compromises the connection between the cuticle and hypodermis, and leads to an increased number of sick and dead worms, indicating essentiality of this module in nematode development and survival. These findings reveal the functional role of nas-33 in nematode molting process and identify astacins as novel anthelmintic targets for parasitic nematodes of socioeconomic significance.

2004 ◽  
Vol 72 (5) ◽  
pp. 2780-2790 ◽  
Author(s):  
Arjan J. van Rossum ◽  
James R. Jefferies ◽  
Frans A. M. Rijsewijk ◽  
E. James LaCourse ◽  
Paul Teesdale-Spittle ◽  
...  

ABSTRACT The phase II detoxification system glutathione transferase (GST) is associated with the establishment of parasitic nematode infections within the gastrointestinal environment of the mammalian host. We report the functional analysis of a GST from an important worldwide parasitic nematode of small ruminants, Haemonchus contortus. This GST shows limited activity with a range of classical GST substrates but effectively binds hematin. The high-affinity binding site for hematin was not present in the GST showing the most identity, CE07055 from the free-living nematode Caenorhabditis elegans. This finding suggests that the high-affinity binding of hematin may represent a parasite adaptation to blood or tissue feeding from the host.


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.


Author(s):  
Janneke Wit ◽  
Clayton Dilks ◽  
Erik Andersen

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.


2021 ◽  
Vol 52 (1) ◽  
Author(s):  
Markéta Zajíčková ◽  
Lukáš Prchal ◽  
Martina Navrátilová ◽  
Nikola Vodvárková ◽  
Petra Matoušková ◽  
...  

AbstractHaemonchus contortus is a parasitic nematode of ruminants which causes significant losses to many farmers worldwide. Since the drugs currently in use for the treatment of haemonchosis are losing their effectiveness due to the drug-resistance of this nematode, a new or repurposed drug is highly needed. As the antipsychotic drug sertraline (SRT) has been shown to be effective against the parasitic nematodes Trichuris muris, Ancylostoma caninum and Schistosoma mansoni, the aim of the present study was to evaluate the possible effect of SRT on H. contortus. The potential hepatotoxicity of SRT was tested in sheep, a common H. contortus host. In addition, the main metabolic pathways of SRT in H. contortus and the ovine liver were identified. While no effect of SRT on H. contortus egg hatching was observed, SRT was found to significantly decrease the viability of H. contortus adults in drug-sensitive and resistant strains, with its effect comparable to the commonly used anthelmintics levamisole and monepantel. Moreover, SRT in anthelmintically active concentrations showed no toxicity to the ovine liver. Biotransformation of SRT in H. contortus was weak, with most of the drug remaining unmetabolized. Production of the main metabolite hydroxy-SRT did not differ significantly between strains. Other minor metabolites such as SRT-O-glucoside, dihydroxy-SRT, and SRT-ketone were also identified in H. contorts adults. Compared to H. contortus, the ovine liver metabolized SRT more extensively, mainly via desmethylation and glucuronidation. In conclusion, the potency of SRT against H. contortus was proven, and it should be tested further toward possible repurposing.


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.


Parasitology ◽  
2006 ◽  
Vol 134 (4) ◽  
pp. 461-482 ◽  
Author(s):  
S. NIKOLAOU ◽  
R. B. GASSER

Signal transduction molecules play key roles in the regulation of developmental processes, such as morphogenesis, organogenesis and cell differentiation in all organisms. They are organized into ‘pathways’ that represent a coordinated network of cell-surface receptors and intracellular molecules, being involved in sensing environmental stimuli and transducing signals to regulate or modulate cellular processes, such as gene expression and cytoskeletal dynamics. A particularly important group of molecules implicated in the regulation of the cytoskeleton for the establishment and maintenance of cell polarity is the PAR proteins (derived from partition defective in asymmetric cell division). The present article reviews salient aspects of PAR proteins involved in the early embryonic development and morphogenesis of the free-living nematode Caenorhabditis elegans and some other organisms, with an emphasis on the molecule PAR-1. Recent advances in the knowledge and understanding of PAR-1 homologues from the economically important parasitic nematode, Haemonchus contortus, of small ruminants is summarized and discussed in the context of exploring avenues for future research in this area for parasitic nematodes.


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.


Author(s):  
Janneke Wit ◽  
Clayton Dilks ◽  
Erik Andersen

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.


Parasitology ◽  
2013 ◽  
Vol 140 (6) ◽  
pp. 683-694 ◽  
Author(s):  
HONGLI ZHANG ◽  
QIANJIN ZHOU ◽  
YI YANG ◽  
XUEQIU CHEN ◽  
BAOLONG YAN ◽  
...  

SUMMARYHaemonchus contortusinfections in small ruminants are of major economic importance worldwide. Heat shock proteins (HSPs) are a family of molecular chaperones that play important roles in the process of invasion and survival of nematodes. Although HSP70 has been identified in several parasitic nematodes, little is known of its distribution and function inHaemonchus contortus. The aims of this study were to characterize HSP70 fromHaemonchus contortus(designed as Hc-hsp70), express Hc-hsp70 and analyse the promoter activity inCaenorhabditis elegans. Bioinformatic analysis revealed that the open reading frame of the Hc-hsp70 cDNA encodes a 646-amino acid peptide, which is highly conserved in comparison to HSP70 in other nematodes. Phylogenetic analysis indicated thatH. contortusis closely related toCaenorhabditis. The 5′-flanking region promoted green fluorescence protein (GFP) expression in the intestine in all larval stages and adult with 2 expression patterns inC. elegans. Expression of Hc-hsp70 mRNA transcripts inC. elegansincreased following 2, 4, 6 h of heat shock and peaked at 4 h. However, its expression induced down-regulation ofhsp-1ofC. elegans. These results suggest that theH. contortushsp70 might have a similar function to that ofC. elegans hsp-1.


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