Elucidating the molecular and developmental biology of parasitic nematodes: Moving to a multiomics paradigm

Ma, Guorong; Wang, Tao; Korhonen, Pasi K.; Hofmann, Andreas; Sternberg, Paul W.; Young, Neil D.; Gasser, Robin B.

doi:10.1016/bs.apar.2019.12.005

Cited by 19 publications

(14 citation statements)

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“…Therefore, integrating multiple omics datasets might be an efficient way to link biochemistry and molecular biology to phenotypes (e.g. virulence and resistance) [ 51 ]. In the present study, although thousands of mutations/variations were identified in protein-coding genes, and substantial changes were indicated in protein abundances, by in-depth integration only 12 mutations at DNA level were directly linked to protein expression alterations in the resistant clinical isolate of L. donovani (Fig.…”

Section: Discussionmentioning

confidence: 99%

Integrative genomic, proteomic and phenotypic studies of Leishmania donovani strains revealed genetic features associated with virulence and antimony-resistance

Zheng

Chen

et al. 2020

Parasites Vectors

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Background Leishmaniasis is a neglected tropical disease affecting millions of people worldwide. Emerging drug resistance of Leishmania species poses threaten to the effective control and elimination programme of this neglected tropical disease. Methods In this work, we conducted drug-resistance testing, whole genome resequencing and proteome profiling for a recently reported clinical isolate with supposed drug resistance (HCZ), and two reference sensitive strains (DD8 and 9044) of Leishmania donovani, to explore molecular mechanisms underlying drug resistance in this parasite. Results With reference to DD8 and 9044 strains, HCZ isolate showed higher-level virulence and clear resistance to antimonials in promastigote culture, infected macrophages and animal experiment. Pairwise genomic comparisons revealed genetic variations (86 copy number variations, 271 frameshift mutations in protein-coding genes and two site mutations in non-coding genes) in HCZ isolate that were absent from the reference sensitive strains. Proteomic analysis indicated different protein expression between HCZ isolate and reference strains, including 69 exclusively detected proteins and 82 consistently down-/upregulated molecules in the HCZ isolate. Integrative analysis showed linkage of 12 genomic variations (gene duplication, insertion and deletion) and their protein expression changes in HCZ isolate, which might be associated with pathogenic and antimony-resistant phenotype. Functional annotation analyses further indicated that molecules involved in nucleotide-binding, fatty acid metabolism, oxidation-reduction and transport might play a role in host-parasite interaction and drug-resistance. Conclusions This comprehensive integrative work provided novel insights into the genetic basis underlying virulence and resistance, suggesting new aspects to be investigated for a better intervention against L. donovani and associated diseases.

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Section: Discussionmentioning

confidence: 99%

Integrative genomic, proteomic and phenotypic studies of Leishmania donovani strains revealed genetic features associated with virulence and antimony-resistance

Zheng

Chen

et al. 2020

Parasites Vectors

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“…However, there is still a long way to go to achieve a comprehensive appreciation of the complexities involved in these interactions and to apply this fundamental knowledge to achieve applied outcomes, such as the development of new interventions to combat nematode infections or nematodiases. A complementary multi-omics approach [ 13 ] is likely required to achieve a paradigm shift. Here, we discuss some possibilities for future research using high-throughput proteomic methods.…”

Section: Conclusion and Opportunities For Future Researchmentioning

confidence: 99%

“…As the building blocks of cells, proteins directly perform critical biofunctions of genes via enzymatic catalysis, cell signalling, signal transduction as well as protein–molecule (i.e., DNA, lipid, carbohydrate and other protein) interactions. In this postgenomic era, a key research agenda is to reveal the expression patterns and functions of nematode genes in different developmental stages and sexes, and to gain a sound understanding of critical pathways and biological processes that molecules in nematodes are involved in [ 11 , 12 , 13 , 14 ].…”

Section: Introductionmentioning

confidence: 99%

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

Wang

Gasser

2021

Pathogens

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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.

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“…Lipid-derived molecules are involved in a variety of biological functions in parasitic nematodes including metabolism and development, making them of particular interest as potential novel anthelminthics that target parasite fitness and development (Ma et al, 2020). Endocannabinoids are lipid-derived molecules important for metabolic homeostasis and immunity, among other functions, and are produced by both mammals and nematodes (Batugedara et al, 2018).…”

Section: Nematode-derived Molecules Involved In Growth and Metabolismmentioning

confidence: 99%

The Two Faces of Nematode Infection: Virulence and Immunomodulatory Molecules From Nematode Parasites of Mammals, Insects and Plants

2020

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Helminths stage a powerful infection that allows the parasite to damage host tissue through migration and feeding while simultaneously evading the host immune system. This feat is accomplished in part through the release of a diverse set of molecules that contribute to pathogenicity and immune suppression. Many of these molecules have been characterized in terms of their ability to influence the infectious capabilities of helminths across the tree of life. These include nematodes that infect insects, known as entomopathogenic nematodes (EPN) and plants with applications in agriculture and medicine. In this review we will first discuss the nematode virulence factors, which aid parasite colonization or tissue invasion, and cause many of the negative symptoms associated with infection. These include enzymes involved in detoxification, factors essential for parasite development and growth, and highly immunogenic ES proteins. We also explore how these parasites use several classes of molecules (proteins, carbohydrates, and nucleic acids) to evade the host’s immune defenses. For example, helminths release immunomodulatory molecules in extracellular vesicles that may be protective in allergy and inflammatory disease. Collectively, these nematode-derived molecules allow parasites to persist for months or even years in a host, avoiding being killed or expelled by the immune system. Here, we evaluate these molecules, for their individual and combined potential as vaccine candidates, targets for anthelminthic drugs, and therapeutics for allergy and inflammatory disease. Last, we evaluate shared virulence and immunomodulatory mechanisms between mammalian and non-mammalian plant parasitic nematodes and EPNs, and discuss the utility of EPNs as a cost-effective model for studying nematode-derived molecules. Better knowledge of the virulence and immunomodulatory molecules from both entomopathogenic nematodes and soil-based helminths will allow for their use as beneficial agents in fighting disease and pests, divorced from their pathogenic consequences.

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Elucidating the molecular and developmental biology of parasitic nematodes: Moving to a multiomics paradigm

Cited by 19 publications

References 336 publications

Integrative genomic, proteomic and phenotypic studies of Leishmania donovani strains revealed genetic features associated with virulence and antimony-resistance

Integrative genomic, proteomic and phenotypic studies of Leishmania donovani strains revealed genetic features associated with virulence and antimony-resistance

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

The Two Faces of Nematode Infection: Virulence and Immunomodulatory Molecules From Nematode Parasites of Mammals, Insects and Plants

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