Metabolomics in antimicrobial drug discovery

Aminov, Rustam

doi:10.1080/17460441.2022.2113774

Cited by 20 publications

(7 citation statements)

References 100 publications

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“…This has enabled improved clinical trials which has shortened the time needed for drugs to move through the development pipeline. Though metabolomics has been widely used to identify novel antibiotics, it is under explored for identifying β-lactam adjuvants (Tuyiringire et al, 10.3389/fmicb.2022.1092556 Frontiers in Microbiology 15 frontiersin.org 2018; Aminov, 2022). Recently, Campos and Zampieri, had utilized high throughput metabolomic approach to test the activity of 1,279 pharmacologically diverse drugs with no known antibacterial activity on E. coli.…”

Section: Omics Based Approachesmentioning

confidence: 99%

β-Lactam potentiators to re-sensitize resistant pathogens: Discovery, development, clinical use and the way forward

et al. 2023

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β-lactam antibiotics are one of the most widely used and diverse classes of antimicrobial agents for treating both Gram-negative and Gram-positive bacterial infections. The β-lactam antibiotics, which include penicillins, cephalosporins, monobactams and carbapenems, exert their antibacterial activity by inhibiting the bacterial cell wall synthesis and have a global positive impact in treating serious bacterial infections. Today, β-lactam antibiotics are the most frequently prescribed antimicrobial across the globe. However, due to the widespread use and misapplication of β-lactam antibiotics in fields such as human medicine and animal agriculture, resistance to this superlative drug class has emerged in the majority of clinically important bacterial pathogens. This heightened antibiotic resistance prompted researchers to explore novel strategies to restore the activity of β-lactam antibiotics, which led to the discovery of β-lactamase inhibitors (BLIs) and other β-lactam potentiators. Although there are several successful β-lactam-β-lactamase inhibitor combinations in use, the emergence of novel resistance mechanisms and variants of β-lactamases have put the quest of new β-lactam potentiators beyond precedence. This review summarizes the success stories of β-lactamase inhibitors in use, prospective β-lactam potentiators in various phases of clinical trials and the different strategies used to identify novel β-lactam potentiators. Furthermore, this review discusses the various challenges in taking these β-lactam potentiators from bench to bedside and expounds other mechanisms that could be investigated to reduce the global antimicrobial resistance (AMR) burden.

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Section: Omics Based Approachesmentioning

confidence: 99%

β-Lactam potentiators to re-sensitize resistant pathogens: Discovery, development, clinical use and the way forward

et al. 2023

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“…Untargeted metabolomics has played a central role in natural product dereplication as this approach allows rapid and small-scale investigation of natural products, even directly from complex mixtures, such as crude extracts and fractions derived from biota bioactive samples. ,− The advancement of mass spectrometry (MS) instrumentation and chemoinformatic tools is a determinant in the field of untargeted metabolomics. MS/MS fragmentation spectra (MS 2 ) represent the fingerprint of a chemical substance, and this information can be used to scan the chemistry of biodiversity in a rapid and informative way.…”

Section: Introductionmentioning

confidence: 99%

NP³ MS Workflow: An Open-Source Software System to Empower Natural Product-Based Drug Discovery Using Untargeted Metabolomics

Bazzano,

de Felicio,

Alves

et al. 2024

Anal. Chem.

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Natural products (or specialized metabolites) are historically the main source of new drugs. However, the current drug discovery pipelines require miniaturization and speeds that are incompatible with traditional natural product research methods, especially in the early stages of the research. This article introduces the NP3 MS Workflow, a robust open-source software system for liquid chromatography–tandem mass spectrometry (LC–MS/MS) untargeted metabolomic data processing and analysis, designed to rank bioactive natural products directly from complex mixtures of compounds, such as bioactive biota samples. NP3 MS Workflow allows minimal user intervention as well as customization of each step of LC–MS/MS data processing, with diagnostic statistics to allow interpretation and optimization of LC–MS/MS data processing by the user. NP3 MS Workflow adds improved computing of the MS2 spectra in an LC–MS/MS data set and provides tools for automatic [M + H]+ ion deconvolution using fragmentation rules; chemical structural annotation against MS2 databases; and relative quantification of the precursor ions for bioactivity correlation scoring. The software will be presented with case studies and comparisons with equivalent tools currently available. NP3 MS Workflow shows a robust and useful approach to select bioactive natural products from complex mixtures, improving the set of tools available for untargeted metabolomics. It can be easily integrated into natural product-based drug-discovery pipelines and to other fields of research at the interface of chemistry and biology.

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“…Meanwhile, bioinformatics-driven predictions using whole-genome sequencing have uncovered the core BGCs and cryptic metabolites, followed by the integration of high-resolution metabolomics ( 17 ) for specialized metabolite identification. The genome-based bioprospecting ( 17 ) and metabolomics-enabled approaches ( 18 ) opened a new era in natural product drug discovery and development.…”

Section: Introductionmentioning

confidence: 99%

Synergy between Genome Mining, Metabolomics, and Bioinformatics Uncovers Antibacterial Chlorinated Carbazole Alkaloids and Their Biosynthetic Gene Cluster fromStreptomyces tubbatahanensissp. nov., a Novel Actinomycete Isolated from Sulu Sea, Philippines

et al. 2023

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Streptomyces tubbatahanensis DSD3025 T is a novel actinomycete with antibiotic and anticancer activities from Tubbataha Reefs Natural Park, a United Nations Educational, Scientific and Cultural Organization World Heritage Site in Sulu Sea and considered one of the Philippines’ oldest and most-well-protected marine ecosystems. In silico genome mining tools were used to identify putative BGCs that led to the discovery of genes involved in the production of halogenated carbazole alkaloids and new natural products. By integrating bioinformatics-driven genome mining and metabolomics, we unearthed the hidden biosynthetic richness and mined the associated chemical entities from the novel Streptomyces species.

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Metabolomics in antimicrobial drug discovery

Cited by 20 publications

References 100 publications

β-Lactam potentiators to re-sensitize resistant pathogens: Discovery, development, clinical use and the way forward

β-Lactam potentiators to re-sensitize resistant pathogens: Discovery, development, clinical use and the way forward

NP³ MS Workflow: An Open-Source Software System to Empower Natural Product-Based Drug Discovery Using Untargeted Metabolomics

Synergy between Genome Mining, Metabolomics, and Bioinformatics Uncovers Antibacterial Chlorinated Carbazole Alkaloids and Their Biosynthetic Gene Cluster fromStreptomyces tubbatahanensissp. nov., a Novel Actinomycete Isolated from Sulu Sea, Philippines

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Metabolomics in antimicrobial drug discovery

Cited by 20 publications

References 100 publications

β-Lactam potentiators to re-sensitize resistant pathogens: Discovery, development, clinical use and the way forward

β-Lactam potentiators to re-sensitize resistant pathogens: Discovery, development, clinical use and the way forward

NP3 MS Workflow: An Open-Source Software System to Empower Natural Product-Based Drug Discovery Using Untargeted Metabolomics

Synergy between Genome Mining, Metabolomics, and Bioinformatics Uncovers Antibacterial Chlorinated Carbazole Alkaloids and Their Biosynthetic Gene Cluster fromStreptomyces tubbatahanensissp. nov., a Novel Actinomycete Isolated from Sulu Sea, Philippines

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NP³ MS Workflow: An Open-Source Software System to Empower Natural Product-Based Drug Discovery Using Untargeted Metabolomics