Metabolomic profiling of the excretory–secretory products of hookworm and whipworm

Wangchuk, Phurpa; Kouremenos, Konstantinos A.; Eichenberger, Ramon M.; Pearson, Mark S.; Susianto, Atik; Wishart, David S.; McConville, Malcolm J.; Loukas, Alex

doi:10.1007/s11306-019-1561-y

Cited by 34 publications

(66 citation statements)

References 78 publications

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“…Sample derivatisation was performed as reported earlier for the GC-MS metabolomic analysis of ESPs derived from hookworms, whipworms and tapeworms [1,24,25]. The upper aqueous phase composed of 3:1 methanol:water (~900 µL) was aliquoted (50 µL) into a pulled point insert, dried using an evaporator at 30 • C (Christ RVC 2-33 CD, John Morris Scientific Australia) and then anhydrous methanol was added (50 µL).…”

Section: Targeted Analysis Of Polar Metabolites Using Gc-msmentioning

confidence: 99%

“…The chloroform/organic layer of the ESPs and control samples was analysed via a GC-MS protocol described by us earlier [24,25]. In this protocol, the organic/chloroform phase of each biological replicate sample was sealed into GC vials and trans-esterified to generate fatty acid methyl esters.…”

Section: Targeted Analysis Of Medium-long Chain Fatty Acids (Mlcfas) mentioning

confidence: 99%

“…Using previously described LC-MS protocols [24,25], we derivatised a small portion (20 µL) of the organic phase of the ESP extract (prepared using the 'Cryomill extraction method') using a 3-nitrophenylhydrazine (3-NPH), which converted the short chain fatty acids (SCFAs) to their 3-nitrophenylhydrazones. The samples (1 µL in triplicate) were then injected into a Shimadzu LC 30AD-TQ 8060 triple quadrupole mass spectrometer (SHIMADZU Scientific Instruments Inc., Columbia, MD, USA) connected to an Agilent EC-C18 poroshell 120 column (50 mm × 2.1 mm × 2.7 µm).…”

Section: Targeted Analysis Of Short Chain Fatty Acids Using Lc-msmentioning

confidence: 99%

“…Small biomolecules were identified and confirmed according to the metabolomics standard initiative (MSI) definitions of level 1 & level 2 identification [24]. The Metabolomics Australia metabolite spectral library was developed using authentic standards for both GC-MS and LC-MS prior to running the Toxocara samples.…”

Section: Metabolite Identification Standards and Data Analysismentioning

confidence: 99%

“…Four unsaturated fatty acids were also identified in the ESPs, including oleic acid (C18:1 9Z-cis), linoleic acid (C18:2), arachidonic acid (C20:4) and docosahexaenoic acid (C22:6). Anti-inflammatory [24]. It can reduce the level of blood triglycerides in humans, which may reduce the risk of heart disease [32].…”

Section: Medium-long Chain Fatty Acids Identified Using Gc-msmentioning

confidence: 99%

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Excretory/Secretory Metabolome of the Zoonotic Roundworm Parasite Toxocara canis

Wangchuk

Lavers²,

Wishart

et al. 2020

Biomolecules

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Toxocariasis is a zoonotic disease affecting humans that is predominantly caused by Toxocara canis and T. cati, primarily parasites of dogs and cats, respectively. Toxocara generally establishes long-term infections by co-opting its host’s physiological processes, while at the same time exploiting the nutritional environment. Adult stage T. canis reside in the gut of the definitive canine host where they employ a suite of strategies to combat intestinal immune responses by actively producing and releasing excretory-secretory products (ESPs). The protein component of T. canis ESPs has been widely studied, but characterisation of the non-protein ESP complement remains neglected. To characterize the secreted metabolome of Toxocara ESPs and to shed light on the parasite’s metabolic processes, we profiled the ESPs of T. canis using both gas chromatography (GC) and liquid chromatography (LC) mass spectrometry approaches. We successfully identified 61 small molecules, including 41 polar metabolites, 14 medium-long chain fatty acids (MLCFAs) and six short chain fatty acids (SCFAs). We identified talose, stearic acid and isovalerate as the major compounds belonging to the polar, MLCFA and SCFA chemical classes, respectively. Most of the 61 identified metabolites appear to have been produced by T. canis via three distinct metabolic pathways - fatty acid, amino acid and carbohydrate metabolism. The majority of the identified ESPs have known biological properties, especially as immunomodulators. However, there is limited/no information on the biological roles or applications of 31 ESP biomolecules, suggesting that these may have novel activities that merit further investigation.

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Section: Targeted Analysis Of Polar Metabolites Using Gc-msmentioning

confidence: 99%

Section: Targeted Analysis Of Medium-long Chain Fatty Acids (Mlcfas) mentioning

confidence: 99%

Section: Targeted Analysis Of Short Chain Fatty Acids Using Lc-msmentioning

confidence: 99%

Section: Metabolite Identification Standards and Data Analysismentioning

confidence: 99%

Section: Medium-long Chain Fatty Acids Identified Using Gc-msmentioning

confidence: 99%

See 3 more Smart Citations

Excretory/Secretory Metabolome of the Zoonotic Roundworm Parasite Toxocara canis

Wangchuk

Lavers²,

Wishart

et al. 2020

Biomolecules

Self Cite

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Taenia solium cysticerci's extracellular vesicles Attenuate the AKT/mTORC1 pathway for Alleviating DSS‐induced colitis in a murine model

Rawat,

Keshri,

Arora

et al. 2024

J of Extracellular Vesicle

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The excretory–secretory proteome plays a pivotal role in both intercellular communication during disease progression and immune escape mechanisms of various pathogens including cestode parasites like Taenia solium. The cysticerci of T. solium causes infection in the central nervous system known as neurocysticercosis (NCC), which affects a significant population in developing countries. Extracellular vesicles (EVs) are 30–150‐nm‐sized particles and constitute a significant part of the secretome. However, the role of EV in NCC pathogenesis remains undetermined. Here, for the first time, we report that EV from T. solium larvae is abundant in metabolites that can negatively regulate PI3K/AKT pathway, efficiently internalized by macrophages to induce AKT and mTOR degradation through auto‐lysosomal route with a prominent increase in the ubiquitination of both proteins. This results in less ROS production and diminished bacterial killing capability among EV‐treated macrophages. Due to this, both macro‐autophagy and caspase‐linked apoptosis are upregulated, with a reduction of the autophagy substrate sequestome 1. In summary, we report that T. solium EV from viable cysts attenuates the AKT–mTOR pathway thereby promoting apoptosis in macrophages, and this may exert immunosuppression during an early viable stage of the parasite in NCC, which is primarily asymptomatic. Further investigation on EV‐mediated immune suppression revealed that the EV can protect the mice from DSS‐induced colitis and improve colon architecture. These findings shed light on the previously unknown role of T. solium EV and the therapeutic role of their immune suppression potential.

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Immune Regulatory Roles of Cells Expressing Taste Signaling Elements in Nongustatory Tissues

Wang

Matsumoto

Jiang

2021

The Pharmacology of Taste

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Metabolomic profiling of the excretory–secretory products of hookworm and whipworm

Cited by 34 publications

References 78 publications

Excretory/Secretory Metabolome of the Zoonotic Roundworm Parasite Toxocara canis

Excretory/Secretory Metabolome of the Zoonotic Roundworm Parasite Toxocara canis

Taenia solium cysticerci's extracellular vesicles Attenuate the AKT/mTORC1 pathway for Alleviating DSS‐induced colitis in a murine model

Immune Regulatory Roles of Cells Expressing Taste Signaling Elements in Nongustatory Tissues

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