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Functional metabolomics: from biomarker discovery to metabolome reprogramming.

Peng B, Li H, Peng XX - Protein Cell (2015)

Bottom Line: Metabolomics is emerging as a powerful tool for studying metabolic processes, identifying crucial biomarkers responsible for metabolic characteristics and revealing metabolic mechanisms, which construct the content of discovery metabolomics.The striking feature on the similarity of the basic metabolic pathways and components among vastly different species makes the reprogramming metabolomics possible when the engineered metabolites play biological roles in cellular activity as a substrate of enzymes and a regulator to other molecules including proteins.This review introduces the current state and trends of discovery metabolomics and reprogramming metabolomics and highlights the importance of reprogramming metabolomics.

View Article: PubMed Central - PubMed

Affiliation: Molecular Foundry, Lawrence Berkeley National Laboratory, Berkeley, CA, 94720, USA.

ABSTRACT
Metabolomics is emerging as a powerful tool for studying metabolic processes, identifying crucial biomarkers responsible for metabolic characteristics and revealing metabolic mechanisms, which construct the content of discovery metabolomics. The crucial biomarkers can be used to reprogram a metabolome, leading to an aimed metabolic strategy to cope with alteration of internal and external environments, naming reprogramming metabolomics here. The striking feature on the similarity of the basic metabolic pathways and components among vastly different species makes the reprogramming metabolomics possible when the engineered metabolites play biological roles in cellular activity as a substrate of enzymes and a regulator to other molecules including proteins. The reprogramming metabolomics approach can be used to clarify metabolic mechanisms of responding to changed internal and external environmental factors and to establish a framework to develop targeted tools for dealing with the changes such as controlling and/or preventing infection with pathogens and enhancing host immunity against pathogens. This review introduces the current state and trends of discovery metabolomics and reprogramming metabolomics and highlights the importance of reprogramming metabolomics.

No MeSH data available.


Related in: MedlinePlus

Antibiotic-resistant metabolome is reprogrammed to antibiotic-susceptible metabolome by exogenous alanine, fructose and glucose. These exogenous metabolites promote TCA flux, increase proton-motive force and lead to kanamycin uptake
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Fig1: Antibiotic-resistant metabolome is reprogrammed to antibiotic-susceptible metabolome by exogenous alanine, fructose and glucose. These exogenous metabolites promote TCA flux, increase proton-motive force and lead to kanamycin uptake

Mentions: Bacterial antibiotic resistance is a threat to human health and to the viability of animal and plant species in the human food chain (Li et al., 2012; Lin et al., 2014). However, novel drugs that can manage infections by multidrug-resistant bacteria have proved elusive. We demonstrated that the bacterial susceptibility to antibiotics was strongly associated with metabolic states, and that specific metabolic profiles were correlating with certain antibiotic-resistance. Glucose, fructose and alanine abundances are greatly suppressed in kanamycin-resistant Edwardsiella tarda revealed by GC/MS based metabolomics. Exogenous alanine, glucose or fructose restores susceptibility of multidrug-resistant E. tarda to killing by kanamycin. Similar results were obtained with other Gram-negative bacteria including Vibrio parahaemolyticus, Klebsiella pneumoniae, Pseudomonas aeruginosa and Gram-positive bacterium Staphylococcus aureus. These results were also reproduced in a mouse model for urinary tract infection. Therefore, metabolites that reverted the metabolomics profile of an antibiotic-resistant strain to that of an antibiotic-sensitive strain could potentially revert the antibiotic resistance (Fig. 1) (Peng et al., 2015a; Su et al., 2015). The study proposes a novel approach to identify metabolic modulator through investigation of metabolomics, by which crucial modulators can be used for therapeutic purpose through reprogramming metabolome (Bhargava and Collins, 2015).Figure 1


Functional metabolomics: from biomarker discovery to metabolome reprogramming.

Peng B, Li H, Peng XX - Protein Cell (2015)

Antibiotic-resistant metabolome is reprogrammed to antibiotic-susceptible metabolome by exogenous alanine, fructose and glucose. These exogenous metabolites promote TCA flux, increase proton-motive force and lead to kanamycin uptake
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4537470&req=5

Fig1: Antibiotic-resistant metabolome is reprogrammed to antibiotic-susceptible metabolome by exogenous alanine, fructose and glucose. These exogenous metabolites promote TCA flux, increase proton-motive force and lead to kanamycin uptake
Mentions: Bacterial antibiotic resistance is a threat to human health and to the viability of animal and plant species in the human food chain (Li et al., 2012; Lin et al., 2014). However, novel drugs that can manage infections by multidrug-resistant bacteria have proved elusive. We demonstrated that the bacterial susceptibility to antibiotics was strongly associated with metabolic states, and that specific metabolic profiles were correlating with certain antibiotic-resistance. Glucose, fructose and alanine abundances are greatly suppressed in kanamycin-resistant Edwardsiella tarda revealed by GC/MS based metabolomics. Exogenous alanine, glucose or fructose restores susceptibility of multidrug-resistant E. tarda to killing by kanamycin. Similar results were obtained with other Gram-negative bacteria including Vibrio parahaemolyticus, Klebsiella pneumoniae, Pseudomonas aeruginosa and Gram-positive bacterium Staphylococcus aureus. These results were also reproduced in a mouse model for urinary tract infection. Therefore, metabolites that reverted the metabolomics profile of an antibiotic-resistant strain to that of an antibiotic-sensitive strain could potentially revert the antibiotic resistance (Fig. 1) (Peng et al., 2015a; Su et al., 2015). The study proposes a novel approach to identify metabolic modulator through investigation of metabolomics, by which crucial modulators can be used for therapeutic purpose through reprogramming metabolome (Bhargava and Collins, 2015).Figure 1

Bottom Line: Metabolomics is emerging as a powerful tool for studying metabolic processes, identifying crucial biomarkers responsible for metabolic characteristics and revealing metabolic mechanisms, which construct the content of discovery metabolomics.The striking feature on the similarity of the basic metabolic pathways and components among vastly different species makes the reprogramming metabolomics possible when the engineered metabolites play biological roles in cellular activity as a substrate of enzymes and a regulator to other molecules including proteins.This review introduces the current state and trends of discovery metabolomics and reprogramming metabolomics and highlights the importance of reprogramming metabolomics.

View Article: PubMed Central - PubMed

Affiliation: Molecular Foundry, Lawrence Berkeley National Laboratory, Berkeley, CA, 94720, USA.

ABSTRACT
Metabolomics is emerging as a powerful tool for studying metabolic processes, identifying crucial biomarkers responsible for metabolic characteristics and revealing metabolic mechanisms, which construct the content of discovery metabolomics. The crucial biomarkers can be used to reprogram a metabolome, leading to an aimed metabolic strategy to cope with alteration of internal and external environments, naming reprogramming metabolomics here. The striking feature on the similarity of the basic metabolic pathways and components among vastly different species makes the reprogramming metabolomics possible when the engineered metabolites play biological roles in cellular activity as a substrate of enzymes and a regulator to other molecules including proteins. The reprogramming metabolomics approach can be used to clarify metabolic mechanisms of responding to changed internal and external environmental factors and to establish a framework to develop targeted tools for dealing with the changes such as controlling and/or preventing infection with pathogens and enhancing host immunity against pathogens. This review introduces the current state and trends of discovery metabolomics and reprogramming metabolomics and highlights the importance of reprogramming metabolomics.

No MeSH data available.


Related in: MedlinePlus