ArticleNature communications2018
The evolution of substrate discrimination in macrolide antibiotic resistance enzymes.
Article in Nature communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
39 citing papers in PubMed, 81 citations in OpenAlex.
- Genetic Characteristics Associated with Probiotic Functions in Four Indonesian Skin Microbiome-Derived Bacterial Strains.Microorganisms · 2026Article
- YTHDF2 regulates the adriamycin (ADM) resistance in NKTCL by modulating the m6A modification of SLC16A9.Translational oncology · 2025Article
- Antechodynamics and Antechokinetics: Dynamics and Kinetics of Antibiotic Resistance Biomolecules.Biomolecules · 2025Review
- Molecular and Phenotypic Evaluation of Antibiotic Resistance in Enteric Rods Isolated from the Oral Cavity.Antibiotics (Basel, Switzerland) · 2025Article
- Nanoarchitectonics of a covalent organic supramolecular cage (COSC) for fluorescent visual detection of macrolides.RSC advances · 2025Article
- Profiling the resistome and virulome of Bacillus strains used for probiotic-based sanitation: a multicenter WGS analysis.BMC genomics · 2025Article
- Comprehensive Genomic Analysis ofMicroorganisms · 2025Article
- CARPDM: cost-effective antibiotic resistome profiling of metagenomic samples using targeted enrichment.Applied and environmental microbiology · 2025Article
- Antibiotic Resistance Gene Expression in Veterinary Probiotics: Two Sides of the Coin.Veterinary sciences · 2025Review
- Global distribution of α/β hydrolase family macrolide esterases in Gram-positive bacteria.The ISME journal · 2025Article
- Geography, Antimicrobial Resistance, and Genomics ofMicroorganisms · 2024Article
- Comprehensive Metagenomic Analysis of Veterinary Probiotics in Broiler Chickens.Animals : an open access journal from MDPI · 2024Article
- Unravelling the mechanisms of antibiotic and heavy metal resistance co-selection in environmental bacteria.FEMS microbiology reviews · 2024Review
- Multidrug resistance in pathogenicFrontiers in veterinary science · 2024Article
- Discovery and characterization of genes conferring natural resistance to the antituberculosis antibiotic capreomycin.Communications biology · 2023Article
- Antibiotic Potentiation as a Promising Strategy to Combat Macrolide Resistance in Bacterial Pathogens.Antibiotics (Basel, Switzerland) · 2023Review
- Quantum chemical investigation of predominant conformation of the antibiotic azithromycin in water and DMSO solutions: thermodynamic and NMR analysis.Royal Society open science · 2023Article
- Extensive screening reveals previously undiscovered aminoglycoside resistance genes in human pathogens.Communications biology · 2023Article
- Structure-Based Design of Bisubstrate Tetracycline Destructase Inhibitors That Block Flavin Redox Cycling.Journal of medicinal chemistry · 2023Article
- The role of adjuvants in overcoming antibacterial resistance due to enzymatic drug modification.RSC medicinal chemistry · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
The production of antibiotics by microbes in the environment and their use in medicine and agriculture select for existing and emerging resistance. To address this inevitability, prudent development of antibiotic drugs requires careful consideration of resistance evolution. Here, we identify the molecular basis for expanded substrate specificity in MphI, a macrolide kinase (Mph) that does not confer resistance to erythromycin, in contrast to other known Mphs. Using a combination of phylogenetics, drug-resistance phenotypes, and in vitro enzyme assays, we find that MphI and MphK phosphorylate erythromycin poorly resulting in an antibiotic-sensitive phenotype. Using likelihood reconstruction of ancestral sequences and site-saturation combinatorial mutagenesis, supported by Mph crystal structures, we determine that two non-obvious mutations in combination expand the substrate range. This approach should be applicable for studying the functional evolution of any antibiotic resistance enzyme and for evaluating the evolvability of resistance enzymes to new generations of antibiotic scaffolds.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.