ArticleProceedings of the National Academy of Sciences of the United States of America2013
Antimicrobial drug resistance affects broad changes in metabolomic phenotype in addition to secondary metabolism.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 94 citations in OpenAlex.
- Sustainable Biocatalytic Cascades: A Versatile Tool in the Synthesis of Natural Products With Therapeutic Potential.Chembiochem : a European journal of chemical biology · 2026Review
- Accumulation of Histidine Reduce the Susceptibility of Vibrio splendidus Persister Cells to Tetracycline.Environmental microbiology reports · 2026Article
- Discovery of natural products that modulate signaling in patient-derived cells.RSC chemical biology · 2026Article
- LC-MS/MS metabolomics unravels the resistant phenotype of carbapenemase-producing Enterobacterales.Metabolomics : Official journal of the Metabolomic Society · 2025Article
- Microbial responses to antibiotics cryptically shift the direction of disease outcomes.Scientific reports · 2025Article
- Unlocking hidden treasures: the evolution of high-throughput mass spectrometry in screening for cryptic natural products.Natural product reports · 2025Review
- Cohort Profile: Guangzhou Nutrition and Health Study (GNHS): A Population-based Multi-omics Study.Journal of epidemiology · 2024Article
- Review
- Advances in Mass Spectrometry-Metabolomics Based Approaches.Advances in experimental medicine and biology · 2023Article
- Genome-scale metabolic modeling in antimicrobial pharmacology.Engineering microbiology · 2022Review
- Article
- Human Gut Antibiotic Resistome and Progression of Diabetes.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- Guidelines for metabolomics-guided transposon mutagenesis for microbial natural product discovery.Methods in enzymology · 2022Article
- Central carbon metabolism remodeling as a mechanism to develop drug tolerance and drug resistance inFrontiers in cellular and infection microbiology · 2022Review
- A Natural Product Chemist's Guide to Unlocking Silent Biosynthetic Gene Clusters.Annual review of biochemistry · 2021Review
- Synergizing the potential of bacterial genomics and metabolomics to find novel antibiotics.Chemical science · 2021Review
- Exogenous Citrulline and Glutamine Contribute to Reverse the Resistance ofFrontiers in microbiology · 2021Article
- Lipid A profiling and metabolomics analysis of paired polymyxin-susceptible and -resistant MDR Klebsiella pneumoniae clinical isolates from the same patients before and after colistin treatment.The Journal of antimicrobial chemotherapy · 2020Article
- Proteomics and metabolomics analysis reveal potential mechanism of extended-spectrum β-lactamase production inRSC advances · 2020Article
- Spatiochemically Profiling Microbial Interactions with Membrane Scaffolded Desorption Electrospray Ionization-Ion Mobility-Imaging Mass Spectrometry and Unsupervised Segmentation.Analytical chemistry · 2019Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Bacteria develop resistance to many classes of antibiotics vertically, by engendering mutations in genes encoding transcriptional and translational apparatus. These severe adaptations affect global transcription, translation, and the correspondingly affected metabolism. Here, we characterize metabolome scale changes in transcriptional and translational mutants in a genomically characterized Nocardiopsis, a soil-derived actinomycete, in stationary phase. Analysis of ultra-performance liquid chromatography-ion mobility-mass spectrometry metabolomic features from a cohort of streptomycin- and rifampicin-resistant mutants grown in the absence of antibiotics exhibits clear metabolomic speciation, and loadings analysis catalogs a marked change in metabolic phenotype. Consistent with derepression, up to 311 features are observed in antibiotic-resistant mutants that are not detected in their progenitors. Mutants demonstrate changes in primary metabolism, such as modulation of fatty acid composition and the increased production of the osmoprotectant ectoine, in addition to the presence of abundant emergent potential secondary metabolites. Isolation of three of these metabolites followed by structure elucidation demonstrates them to be an unusual polyketide family with a previously uncharacterized xanthene framework resulting from sequential oxidative carbon skeletal rearrangements. Designated as "mutaxanthenes," this family can be correlated to a type II polyketide gene cluster in the producing organism. Taken together, these data suggest that biosynthetic pathway derepression is a general consequence of some antibiotic resistance mutations.
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