Metabolomics: Eavesdropping on silent conversations between hosts and their unwelcome guests

Newsom, Sydney; McCall, Laura-Isobel

doi:10.1371/journal.ppat.1006926

Cited by 14 publications

(5 citation statements)

References 25 publications

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“…Indeed, unlike mass spectrometry imaging approaches, liquid chromatography-mass spectrometry does not inherently preserve spatial information 10 . Chemical cartography approaches bridge this gap by including sampling location at the time of project conceptualization, in the sample metadata, and at data processing steps.…”

Section: Discussionmentioning

confidence: 99%

Chemical Cartography Approaches to Study Trypanosomatid Infection

Dean

Haffner

Katemauswa

et al. 2022

JoVE

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Pathogen tropism and disease tropism refer to the tissue locations selectively colonized or damaged by pathogens, leading to localized disease symptoms. Humaninfective trypanosomatid parasites include Trypanosoma cruzi, the causative agent of Chagas disease; Trypanosoma brucei, the causative agent of sleeping sickness; and Leishmania species, causative agents of leishmaniasis. Jointly, they affect 20 million people across the globe. These parasites show specific tropism: heart, esophagus, colon for T. cruzi, adipose tissue, pancreas, skin, circulatory system and central nervous system for T. brucei, skin for dermotropic Leishmania strains, and liver, spleen, and bone marrow for viscerotropic Leishmania strains. A spatial perspective is therefore essential to understand trypanosomatid disease pathogenesis. Chemical cartography generates 3D visualizations of small molecule abundance generated via liquid chromatography-mass spectrometry, in comparison to microbiological and immunological parameters. This protocol demonstrates how chemical cartography can be applied to study pathogenic processes during trypanosomatid infection, beginning from systematic tissue sampling and metabolite extraction, followed by liquid chromatography-tandem mass spectrometry data acquisition, and concluding with the generation of 3D maps of metabolite distribution. This method can be used for multiple research questions, such as nutrient requirements for tissue colonization by T. cruzi, T. brucei, or Leishmania, immunometabolism at sites of infection, and the relationship between local tissue metabolic perturbation and clinical disease symptoms, leading to comprehensive insight into trypanosomatid disease pathogenesis.

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Section: Discussionmentioning

confidence: 99%

Chemical Cartography Approaches to Study Trypanosomatid Infection

Dean

Haffner

Katemauswa

et al. 2022

JoVE

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“…The metabolome provides a link between genotype and phenotype by identifying changes occurring at the molecular level, for example, when parasites and their hosts interact [ 16 ]. Metabolism is also an indicator of the host physiological state.…”

Section: Discussionmentioning

confidence: 99%

Dysregulation of Glycerophosphocholines in the Cutaneous Lesion Caused by Leishmania major in Experimental Murine Models

et al. 2021

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Cutaneous leishmaniasis (CL) is the most common disease form caused by a Leishmania parasite infection and considered a neglected tropical disease (NTD), affecting 700,000 to 1.2 million new cases per year in the world. Leishmania major is one of several different species of the Leishmania genus that can cause CL. Current CL treatments are limited by adverse effects and rising resistance. Studying disease metabolism at the site of infection can provide knowledge of new targets for host-targeted drug development. In this study, tissue samples were collected from mice infected in the ear or footpad with L. major and analyzed by untargeted liquid chromatography-tandem mass spectrometry (LC-MS/MS). Significant differences in overall metabolite profiles were noted in the ear at the site of the lesion. Interestingly, lesion-adjacent, macroscopically healthy sites also showed alterations in specific metabolites, including selected glycerophosphocholines (PCs). Host-derived PCs in the lower m/z range (m/z 200–799) showed an increase with infection in the ear at the lesion site, while those in the higher m/z range (m/z 800–899) were decreased with infection at the lesion site. Overall, our results expanded our understanding of the mechanisms of CL pathogenesis through host metabolism and may lead to new curative measures against infection with Leishmania.

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“…To overcome this limitation, the field of infection metabolomics is evolving to access the opportunities of metabolic biomarkers, as the sensitivity of a metabolite profile greatly reflects adaptation to the surrounding microenvironment. One solution to differentiate host-pathogen metabolites is the integration of other omics technologies to correlate metabolite abundance to gene expression or protein production ( 124 ). Despite the development and increased accessibility of high-throughput sequencing and MS technology, there is still a high cost associated with the processing and measuring of large data sets, especially for dual-organism studies.…”

Section: Outlooks and Perspectivesmentioning

confidence: 99%

Fun(gi)omics: Advanced and Diverse Technologies to Explore Emerging Fungal Pathogens and Define Mechanisms of Antifungal Resistance

Ball

Langille

Geddes‐McAlister

2020

mBio

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The landscape of infectious fungal agents includes previously unidentified or rare pathogens with the potential to cause unprecedented casualties in biodiversity, food security, and human health. The influences of human activity, including the crisis of climate change, along with globalized transport, are underlying factors shaping fungal adaptation to increased temperature and expanded geographical regions. Furthermore, the emergence of novel antifungal-resistant strains linked to excessive use of antifungals (in the clinic) and fungicides (in the field) offers an additional challenge to protect major crop staples and control dangerous fungal outbreaks. Hence, the alarming frequency of fungal infections in medical and agricultural settings requires effective research to understand the virulent nature of fungal pathogens and improve the outcome of infection in susceptible hosts. Mycology-driven research has benefited from a contemporary and unified approach of omics technology, deepening the biological, biochemical, and biophysical understanding of these emerging fungal pathogens. Here, we review the current state-of-the-art multi-omics technologies, explore the power of data integration strategies, and highlight discovery-based revelations of globally important and taxonomically diverse fungal pathogens. This information provides new insight for emerging pathogens through an in-depth understanding of well-characterized fungi and provides alternative therapeutic strategies defined through novel findings of virulence, adaptation, and resistance.

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Metabolomics: Eavesdropping on silent conversations between hosts and their unwelcome guests

Cited by 14 publications

References 25 publications

Chemical Cartography Approaches to Study Trypanosomatid Infection

Chemical Cartography Approaches to Study Trypanosomatid Infection

Dysregulation of Glycerophosphocholines in the Cutaneous Lesion Caused by Leishmania major in Experimental Murine Models

Fun(gi)omics: Advanced and Diverse Technologies to Explore Emerging Fungal Pathogens and Define Mechanisms of Antifungal Resistance

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