ArticleAntimicrobial agents and chemotherapy2016
Potential of Tetracycline Resistance Proteins To Evolve Tigecycline Resistance.
Article in Antimicrobial agents and chemotherapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 99 papers, 1 of them a synthesis that pooled it.
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Who cites it
99 citing papers in PubMed, 1 synthesis or guideline pooled it, 176 citations in OpenAlex.
- Antimicrobial resistance in Clostridioides (Clostridium) difficile derived from humans: a systematic review and meta-analysis.Antimicrobial resistance and infection control · 2020Pooled it
- Emergence and dissemination of extensively drug-resistant ST307Microbial genomics · 2026Article
- Phylogenetic diversification and fitness trade-offs of TetA variants in mediating eravacycline resistance inAntimicrobial agents and chemotherapy · 2026Article
- A novel self-transmissible mega plasmid from extensively drug-resistantCurrent research in microbial sciences · 2026Article
- Antimicrobial susceptibility and virulence traits ofFrontiers in microbiology · 2026Article
- Omadacycline Pharmacokinetics: Characteristics, Contributing Factors, and Clinical Significance.Drugs in R&D · 2025Review
- Rapid replacement of blaKPC variant in ST11 carbapenem-resistant and hypervirulent Klebsiella pneumoniae contributed to ceftazidime/avibactam resistance during severe in vivo infection.The Journal of antimicrobial chemotherapy · 2025Article
- Prevalence, toxin virulence genes and investigating the effect of mutations in the tetracycline gene (tetK) on the response of methicillin-resistant Staphylococcus aureus to antibiotics: a study in sickle cell disease patients in Riyadh, Saudi Arabia.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2025Article
- Molecular Epidemiology ofAntibiotics (Basel, Switzerland) · 2025Article
- Genomic characterization of antimicrobial resistance and mobile genetic elements in swine gut bacteria isolated from a Canadian research farm.Animal microbiome · 2025Article
- Genomic Diversity of theMicroorganisms · 2025Article
- Traditional marketed meats as a reservoir of multidrug-resistant Escherichia coli.International microbiology : the official journal of the Spanish Society for Microbiology · 2025Article
- Minocycline Susceptibility of Carbapenem-ResistantInfection & chemotherapy · 2025Article
- The tetracycline resistome is shaped by selection for specific resistance mechanisms by each antibiotic generation.Nature communications · 2025Article
- An evolved, orthogonal ssDNA generator for targeted hypermutation of multiple genomic loci.Nucleic acids research · 2025Article
- The investigation of molecular epidemiological characteristics and resistance mechanism of tigecycline resistantFrontiers in cellular and infection microbiology · 2025Article
- Article
- Commercial Day-Old Chicks in Nigeria Are Potential Reservoirs of Colistin- and Tigecycline-Resistant Potentially PathogenicAntibiotics (Basel, Switzerland) · 2024Article
- Antibiotic resistance mediated by gene amplifications.npj antimicrobials and resistance · 2024Review
- Review
39 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tigecycline is a glycylcycline antibiotic active against multidrug-resistant bacterial pathogens. The objectives of our study were to examine the potential of the Tet(A), Tet(K), Tet(M), and Tet(X) tetracycline resistance proteins to acquire mutations causing tigecycline resistance and to determine how this affects resistance to earlier classes of tetracyclines. Mutations in all four tet genes caused a significant increase in the tigecycline MIC in Escherichia coli, and strains expressing mutant Tet(A) and Tet(X) variants reached clinically relevant MICs (2 mg/liter and 3 mg/liter, respectively). Mutations predominantly accumulated in transmembrane domains of the efflux pumps, most likely increasing the accommodation of tigecycline as a substrate. All selected Tet(M) mutants contained at least one mutation in the functionally most important loop III of domain IV. Deletion of leucine 505 of this loop led to the highest increase of the tigecycline MIC (0.5 mg/liter) among Tet(M) mutants. It also caused collateral sensitivity to earlier classes of tetracyclines. A majority of the Tet(X) mutants showed increased activity against all three classes of tetracylines. All tested Tet proteins have the potential to acquire mutations leading to increased MICs of tigecycline. As tet genes are widely found in pathogenic bacteria and spread easily by horizontal gene transfer, resistance development by alteration of existing Tet proteins might compromise the future medical use of tigecycline. We predict that Tet(X) might become the most problematic future Tet determinant, since its weak intrinsic tigecycline activity can be mutationally improved to reach clinically relevant levels without collateral loss in activity to other tetracyclines.
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