Combined Untargeted and Targeted Metabolomics Approaches Reveal Urinary Changes of Amino Acids and Energy Metabolism in Canine Babesiosis With Different Levels of Kidney Function

Kuleš, Josipa; Rubić, Ivana; Ljubić, Blanka Beer; Bilić, Petra; Rafaj, Renata Barić; Brkljačić, Mirna; Burchmore, Richard; Eckersall, David; Mrljak, Vladimir

doi:10.3389/fmicb.2021.715701

Cited by 13 publications

(11 citation statements)

References 111 publications

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“…Other signi cantly affected pathways were related to lipid metabolism, and included proteins such as apolipoproteins (apoA-I, apoA-IV, apoB, apoE, apoM, apoH) and plasma retinol-binding protein (RBP4). A link between babesiosis and lipid metabolism in the host has already been documented by transcriptomics, proteomics, and metabolomics studies 20,44,45 . The importance of lipid metabolism in babesiosis is suggested to be related to the catabolic reaction during the acute phase response in the host.…”

Section: Proteomic Pro Ling Between Control Group Uncomplicated and C...mentioning

confidence: 85%

Serum proteome profiling of naturally acquired Babesia rossi infection in dogs

Kuleš

Rubić

Farkaš

et al. 2023

Preprint

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Babesiosis is a disease of significant veterinary importance with worldwide distribution. It is caused by intra-erythrocyte protozoal parasites, with Babesia rossi causing the most severe clinical signs of all the large Babesia parasites infecting dogs. The disease can be clinically classified into uncomplicated and complicated forms with a wide range of clinical presentations from a mild, subclinical illness to complicated forms and death. The aim of this study was to assess serum proteomic profiles from dogs with babesiosis and healthy dogs using a label-based proteomics approach. Altogether 32 dogs naturally infected with B. rossi (subdivided into 18 uncomplicated cases and 14 complicated cases of babesiosis) and 20 healthy dogs were included. There were 78 proteins with significantly different abundances between the three groups of dogs. Elucidation of proteins and pathways involved in canine babesiosis caused by B. rossi have revealed key differences associated with haemostasis, innate immune system, lipid metabolism and inflammation. Shotgun proteomic profiling allowed identification of potential serum biomarkers for differentiation of disease severity in canine babesiosis caused by B. rossi. These findings may be applicable to the study of host-parasite interactions and the development of novel therapeutic targets.

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Section: Proteomic Pro Ling Between Control Group Uncomplicated and C...mentioning

confidence: 85%

Serum proteome profiling of naturally acquired Babesia rossi infection in dogs

Kuleš

Rubić

Farkaš

et al. 2023

Preprint

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“…There are only a few existing studies of the metabolome of Babesia. Previous investigations assessed differences in the metabolism of free merozoites and infected RBCs (iRBCs) during B. divergens infection and in the urine metabolic profiles of dogs with B. canis infection using metabolomics approaches (Fernańdez-Garcia et al, 2021;Kulešet al, 2021;Beri et al, 2023). Recent research on metabolic profiling was based on erythrocytes separated from B. microti-infected mice and found sabotage of metabolic pathways in iRBCs, including amino acid, lipid, and nucleotide metabolism and the tricarboxylic acid cycle (Gong et al, 2023).…”

Section: Discussionmentioning

confidence: 99%

Serum metabolomic profiles in BALB/c mice induced by Babesia microti infection

Shen¹,

Wang²,

Han³

et al. 2023

Front. Cell. Infect. Microbiol.

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IntroductionThe protozoan parasite Babesia microti is the primary cause of human babesiosis. This parasite invades and multiplies inside red blood cells (RBCs), and infections differ significantly based on the age and immune competency of the host. The aim of this study was to investigate the use of serum metabolic profiling to identify systemic metabolic variations between B. microti-infected mice and noninfected controls.MethodsA serum metabolomics analysis of BALB/c mice that had been intraperitoneally injected with 107B. microti-infected RBCs was performed. Serum samples from the early infected group (2 days postinfection), the acutely infected group (9 days postinfection), and the noninfected group were collected and evaluated using a liquid chromatography−mass spectrometry (LC−MS) platform. Principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA), and orthogonal partial least squares discriminant analysis (OPLS-DA) identified metabolomic profiles that differentiated the B. microti-infected and noninfected groups.ResultsOur results confirm that the serum metabolome is significantly influenced by acute B. microti infection and show that infection results in dysregulation of metabolic pathways and perturbation of metabolites. Acutely infected mice displayed perturbations in metabolites associated with taurine and hypotaurine metabolism, histidine metabolism, and arachidonic acid metabolism. Taurocholic acid, anserine, and arachidonic acid may be potential candidates as serological biomarkers for diagnosing B. microti infection at the acute stage. These metabolites could be further examined for their role in disease complexity.DiscussionOur findings demonstrate that the acute stage of B. microti infection induces abnormalities in the metabolites present in mouse serum and provide new insight into the mechanisms involved in systemic metabolic changes that occur during B. microti infection.

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“…field [27]. Our previous study assessed the urine metabolic profile in dogs with babesiosis using untargeted and targeted MS-based metabolomics approaches, and demonstrated that kidney dysfunction accompanying canine babesiosis was associated with changes in amino acid metabolism, energy metabolism, and fatty acid metabolism [28].…”

Section: The Metabolomics Dataset In Dogs Infected With B Canismentioning

confidence: 99%

Multi Platforms Strategies and Metabolomics Approaches for the Investigation of Comprehensive Metabolite Profile in Dogs with Babesia canis Infection

Rubić

Burchmore

Weidt

et al. 2022

IJMS

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Canine babesiosis is an important tick-borne disease worldwide, caused by parasites of the Babesia genus. Although the disease process primarily affects erythrocytes, it may also have multisystemic consequences. The goal of this study was to explore and characterize the serum metabolome, by identifying potential metabolites and metabolic pathways in dogs naturally infected with Babesia canis using liquid and gas chromatography coupled to mass spectrometry. The study included 12 dogs naturally infected with B. canis and 12 healthy dogs. By combining three different analytical platforms using untargeted and targeted approaches, 295 metabolites were detected. The untargeted ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) metabolomics approach identified 64 metabolites, the targeted UHPLC-MS/MS metabolomics approach identified 205 metabolites, and the GC-MS metabolomics approach identified 26 metabolites. Biological functions of differentially abundant metabolites indicate the involvement of various pathways in canine babesiosis including the following: glutathione metabolism; alanine, aspartate, and glutamate metabolism; glyoxylate and dicarboxylate metabolism; cysteine and methionine metabolism; and phenylalanine, tyrosine, and tryptophan biosynthesis. This study confirmed that host–pathogen interactions could be studied by metabolomics to assess chemical changes in the host, such that the differences in serum metabolome between dogs with B. canis infection and healthy dogs can be detected with liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS) methods. Our study provides novel insight into pathophysiological mechanisms of B. canis infection.

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Combined Untargeted and Targeted Metabolomics Approaches Reveal Urinary Changes of Amino Acids and Energy Metabolism in Canine Babesiosis With Different Levels of Kidney Function

Cited by 13 publications

References 111 publications

Serum proteome profiling of naturally acquired Babesia rossi infection in dogs

Serum proteome profiling of naturally acquired Babesia rossi infection in dogs

Serum metabolomic profiles in BALB/c mice induced by Babesia microti infection

Multi Platforms Strategies and Metabolomics Approaches for the Investigation of Comprehensive Metabolite Profile in Dogs with Babesia canis Infection

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