Changes in amino acids of bile in Fasciola hepatica infections

Isseroff, Hadar; Tunis, Marvin; Read, Clark P.

doi:10.1016/0305-0491(72)90018-1

Cited by 19 publications

(9 citation statements)

References 6 publications

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“…In the present study, the increase of total amino acids in C. sinensis-infected bile was in agreement with a previous study (Table 1) [35]. There might be two possible sources for these biliary amino acids.…”

Section: Discussionsupporting

confidence: 94%

“…Thus, many plasma amino acids, including Ser, Gly, Ala, His, Thr, and Lys, whose concentrations increased in C. sinensis-infected bile (Table 1), would be leaked from the injury of small vessels and blended into the bile [38]. The second possible source of these biliary amino acids might be the digestion of epithelial exfoliations and damaged tissues as well as plasma proteins from the host [35]. Emerging evidences have proven that several secreted proteases of trematodes, such as cysteine peptidases and aminopeptidases, can degrade host tissues, including hemoglobin, plasma, antibodies, and extracellular matrix, to small peptides [39][40][41][42][43].…”

Section: Discussionmentioning

confidence: 99%

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Amino acids serve as an important energy source for adult flukes of Clonorchis sinensis

Chen

Zhou

et al. 2020

PLoS Negl Trop Dis

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Clonorchiasis, caused by chronic infection with Clonorchis sinensis (C. sinensis), is an important food-borne parasitic disease that seriously afflicts more than 35 million people globally, resulting in a socioeconomic burden in endemic regions. C. sinensis adults longterm inhabit the microaerobic and limited-glucose environment of the bile ducts. Energy metabolism plays a key role in facilitating the adaptation of adult flukes to crowded habitat and hostile environment. To understand energy source for adult flukes, we compared the component and content of free amino acids between C. sinensis-infected and uninfected bile. The results showed that the concentrations of free amino acids, including aspartic acid, serine, glycine, alanine, histidine, asparagine, threonine, lysine, hydroxylysine, and urea, were significantly higher in C. sinensis-infected bile than those in uninfected bile. Furthermore, exogenous amino acids could be utilized by adult flukes via the gluconeogenesis pathway regardless of the absence or presence of exogenous glucose, and the rate-limiting enzymes, such as C. sinensis glucose-6-phosphatase, fructose-1,6-bisphosphatase, phosphoenolpyruvate carboxykinase, and pyruvate carboxylase, exhibited high expression levels by quantitative real-time PCR analysis. Interestingly, no matter whether exogenous glucose was present, inhibition of gluconeogenesis reduced the glucose and glycogen levels as well as the viability and survival time of adult flukes. These results suggest that gluconeogenesis might play a vital role in energy metabolism of C. sinensis and exogenous amino acids probably serve as an important energy source that benefits the continued survival of adult flukes in the host. Our study will be a cornerstone for illuminating the biological characteristics of C. sinensis and the host-parasite interactions.

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Section: Discussionsupporting

confidence: 94%

Section: Discussionmentioning

confidence: 99%

Amino acids serve as an important energy source for adult flukes of Clonorchis sinensis

Chen

Zhou

et al. 2020

PLoS Negl Trop Dis

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“…Bile duct hyperplasia is a characteristic pathology associated with liver fluke infection and begins prior to the parasite entering the bile ducts. Several decades ago, studies by Isseroff and colleagues [ 60 – 63 ] reported that proline secreted by immature F. hepatica , as early as 25 dpi, stimulates collagen synthesis that results in the bile duct enlargement. Analysis of the immature fluke transcriptome data revealed that the arginine and proline metabolism pathway is amongst the most highly transcribed of the amino acid metabolism pathways.…”

Section: Resultsmentioning

confidence: 99%

Complementary transcriptomic and proteomic analyses reveal the cellular and molecular processes that drive growth and development of Fasciola hepatica in the host liver

et al. 2021

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Background The major pathogenesis associated with Fasciola hepatica infection results from the extensive tissue damage caused by the tunnelling and feeding activity of immature flukes during their migration, growth and development in the liver. This is compounded by the pathology caused by host innate and adaptive immune responses that struggle to simultaneously counter infection and repair tissue damage. Results Complementary transcriptomic and proteomic approaches defined the F. hepatica factors associated with their migration in the liver, and the resulting immune-pathogenesis. Immature liver-stage flukes express ~ 8000 transcripts that are enriched for transcription and translation processes reflective of intensive protein production and signal transduction pathways. Key pathways that regulate neoblast/pluripotent cells, including the PI3K-Akt signalling pathway, are particularly dominant and emphasise the importance of neoblast-like cells for the parasite’s rapid development. The liver-stage parasites display different secretome profiles, reflecting their distinct niche within the host, and supports the view that cathepsin peptidases, cathepsin peptidase inhibitors, saposins and leucine aminopeptidases play a central role in the parasite’s destructive migration, and digestion of host tissue and blood. Immature flukes are also primed for countering immune attack by secreting immunomodulating fatty acid binding proteins (FABP) and helminth defence molecules (FhHDM). Combined with published host microarray data, our results suggest that considerable immune cell infiltration and subsequent fibrosis of the liver tissue exacerbates oxidative stress within parenchyma that compels the expression of a range of antioxidant molecules within both host and parasite. Conclusions The migration of immature F. hepatica parasites within the liver is associated with an increase in protein production, expression of signalling pathways and neoblast proliferation that drive their rapid growth and development. The secretion of a defined set of molecules, particularly cathepsin L peptidases, peptidase-inhibitors, saponins, immune-regulators and antioxidants allow the parasite to negotiate the liver micro-environment, immune attack and increasing levels of oxidative stress. This data contributes to the growing F. hepatica -omics information that can be exploited to understand parasite development more fully and for the design of novel control strategies to prevent host liver tissue destruction and pathology.

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“…Additionally, the presence of the parasite appears to influence the composition of bile acids . Bile acids act as signalling molecules through either TGR5 or FXR to regulate intestinal homeostasis via the inhibition of inflammation, prevention of pathogen invasion and maintenance of tissue integrity .…”

Section: Altered Immune Homeostasis During Fasciola Infectionmentioning

confidence: 99%

A prospective view of animal and human Fasciolosis

Cwiklinski

O’Neill

Donnelly

et al. 2016

Parasite Immunology

171

114

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SummaryFasciolosis, a food‐borne trematodiasis, results following infection with the parasites, Fasciola hepatica and Fasciola gigantica. These trematodes greatly affect the global agricultural community, infecting millions of ruminants worldwide and causing annual economic losses in excess of US $3 billion. Fasciolosis, an important zoonosis, is classified by WHO as a neglected tropical disease with an estimated 17 million people infected and a further 180 million people at risk of infection. The significant impact on agriculture and human health together with the increasing demand for animal‐derived food products to support global population growth demonstrate that fasciolosis is a major One Health problem. This review details the problematic issues surrounding fasciolosis control, including drug resistance, lack of diagnosis and the threat that hybridization of the Fasciola species poses to future animal and human health. We discuss how these parasites may mediate their long‐term survival through regulation and modulation of the host immune system, by altering the host immune homeostasis and/or by influencing the intestinal microbiome particularly in respect to concurrent infections with other pathogens. Large genome, transcriptome and proteomic data sets are now available to support an integrated One Health approach to develop novel diagnostic and control strategies for both animal and human disease.

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Changes in amino acids of bile in Fasciola hepatica infections

Cited by 19 publications

References 6 publications

Amino acids serve as an important energy source for adult flukes of Clonorchis sinensis

Amino acids serve as an important energy source for adult flukes of Clonorchis sinensis

Complementary transcriptomic and proteomic analyses reveal the cellular and molecular processes that drive growth and development of Fasciola hepatica in the host liver

A prospective view of animal and human Fasciolosis

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