Metabolomics in infectious diseases and drug discovery

Tounta, Vivian; Liu, Yi; Cheyne, Ashleigh; Larrouy-Maumus, Gérald

doi:10.1039/d1mo00017a

Cited by 87 publications

(76 citation statements)

References 146 publications

(241 reference statements)

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“…Based on what is observed in other vector-borne viruses, these classes of proteins may be acting in a pro- and antiviral fashion to support the balance between viral propagation and the survival inside host cells, leading to the persistent infection. Additionally, metabolomics studies would provide complementary information regarding subtle metabolic shifts ( Tounta et al., 2021 ). Overall, our data may contribute to a better comprehension of the adaptive molecular mechanisms of Ae.…”

Section: Discussionmentioning

confidence: 99%

Aedes aegypti Aag-2 Cell Proteome Modulation in Response to Chikungunya Virus Infection

Vasconcellos

Melo

Mandacaru

et al. 2022

Front. Cell. Infect. Microbiol.

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Chikungunya virus (CHIKV) is a single-stranded positive RNA virus that belongs to the genus Alphavirus and is transmitted to humans by infected Aedes aegypti and Aedes albopictus bites. In humans, CHIKV usually causes painful symptoms during acute and chronic stages of infection. Conversely, virus–vector interaction does not disturb the mosquito’s fitness, allowing a persistent infection. Herein, we studied CHIKV infection of Ae. aegypti Aag-2 cells (multiplicity of infection (MOI) of 0.1) for 48 h through label-free quantitative proteomic analysis and transmission electron microscopy (TEM). TEM images showed a high load of intracellular viral cargo at 48 h postinfection (hpi), as well as an unusual elongated mitochondria morphology that might indicate a mitochondrial imbalance. Proteome analysis revealed 196 regulated protein groups upon infection, which are related to protein synthesis, energy metabolism, signaling pathways, and apoptosis. These Aag-2 proteins regulated during CHIKV infection might have roles in antiviral and/or proviral mechanisms and the balance between viral propagation and the survival of host cells, possibly leading to the persistent infection.

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Section: Discussionmentioning

confidence: 99%

Aedes aegypti Aag-2 Cell Proteome Modulation in Response to Chikungunya Virus Infection

Vasconcellos

Melo

Mandacaru

et al. 2022

Front. Cell. Infect. Microbiol.

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“…Metabolomics is capable of quantifying all low molecular weight compounds (metabolites; collectively known as the metabolome) in biofluids, cells, tissues, and whole organisms, and is designed to quantitatively analyze and describe molecular phenotypes ( 144 ). Metabolomics is an omics technique that has been adapted for the study of infectious diseases – broadening our knowledge with respect to its use for prognostic and diagnostic purposes, specifically the screening of disease-specific biomarkers ( 145 ). Metabolomics has been, and is still being, used to study the biological mechanisms of TB both in vitro and in vivo , in animal models and human patients ( 146 – 148 ).…”

Section: Using Proteomics and Metabolomics To Understand Tb Granulomasmentioning

confidence: 99%

Tuberculous Granuloma: Emerging Insights From Proteomics and Metabolomics

et al. 2022

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Mycobacterium tuberculosis infection, which claims hundreds of thousands of lives each year, is typically characterized by the formation of tuberculous granulomas — the histopathological hallmark of tuberculosis (TB). Our knowledge of granulomas, which comprise a biologically diverse body of pro- and anti-inflammatory cells from the host immune responses, is based mainly upon examination of lungs, in both human and animal studies, but little on their counterparts from other organs of the TB patient such as the brain. The biological heterogeneity of TB granulomas has led to their diverse, relatively uncoordinated, categorization, which is summarized here. However, there is a pressing need to elucidate more fully the phenotype of the granulomas from infected patients. Newly emerging studies at the protein (proteomics) and metabolite (metabolomics) levels have the potential to achieve this. In this review we summarize the diverse nature of TB granulomas based upon the literature, and amplify these accounts by reporting on the relatively few, emerging proteomics and metabolomics studies on TB granulomas. Metabolites (for example, trimethylamine-oxide) and proteins (such as the peptide PKAp) associated with TB granulomas, and knowledge of their localizations, help us to understand the resultant phenotype. Nevertheless, more multidisciplinary ‘omics studies, especially in human subjects, are required to contribute toward ushering in a new era of understanding of TB granulomas – both at the site of infection, and on a systemic level.

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“…Metabolomics is a relatively new omics approach that aims to characterize the metabolomes, small molecule metabolite profiles, in organisms [ 14 ]. The advantage of metabolomics is that it provides close readouts of organism and cellular phenotypes.…”

Section: Introductionmentioning

confidence: 99%

18β-Glycyrrhetinic Acid Induces Metabolic Changes and Reduces Staphylococcus aureus Bacterial Cell-to-Cell Interactions

et al. 2022

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The rise in bacterial resistance to common antibiotics has raised an increased need for alternative treatment strategies. The natural antibacterial product, 18β-glycyrrhetinic acid (GRA) has shown efficacy against community-associated methicillin-resistant Staphylococcus aureus (MRSA), although its interactions against planktonic and biofilm modes of growth remain poorly understood. This investigation utilized biochemical and metabolic approaches to further elucidate the effects of GRA on MRSA. Prolonged exposure of planktonic MRSA cell cultures to GRA resulted in increased production of staphyloxanthin, a pigment known to exhibit antioxidant and membrane-stabilizing functions. Then, 1D 1H NMR analyses of intracellular metabolite extracts from MRSA treated with GRA revealed significant changes in intracellular polar metabolite profiles, including increased levels of succinate and citrate, and significant reductions in several amino acids, including branch chain amino acids. These changes reflect the MRSA response to GRA exposure, including potentially altering its membrane composition, which consumes branched chain amino acids and leads to significant energy expenditure. Although GRA itself had no significant effect of biofilm viability, it seems to be an effective biofilm disruptor. This may be related to interference with cell–cell aggregation, as treatment of planktonic MRSA cultures with GRA leads to a significant reduction in micro-aggregation. The dispersive nature of GRA on MRSA biofilms may prove valuable for treatment of such infections and could be used to increase susceptibility to complementary antibiotic therapeutics.

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Metabolomics in infectious diseases and drug discovery

Abstract: Metabolomics has emerged as an invaluable tool that can be used along with genomics, transcriptomics and proteomics to understand host-pathogen interactions at small-molecule levels. Metabolomics has been used to study...

Cited by 87 publications

References 146 publications

Aedes aegypti Aag-2 Cell Proteome Modulation in Response to Chikungunya Virus Infection

Aedes aegypti Aag-2 Cell Proteome Modulation in Response to Chikungunya Virus Infection

Tuberculous Granuloma: Emerging Insights From Proteomics and Metabolomics

18β-Glycyrrhetinic Acid Induces Metabolic Changes and Reduces Staphylococcus aureus Bacterial Cell-to-Cell Interactions

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