ArticlePloS one2016
Step-Wise Increase in Tigecycline Resistance in Klebsiella pneumoniae Associated with Mutations in ramR, lon and rpsJ.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 50 citations in OpenAlex.
- Heteroresistance is associated with mutations during low concentration of tigecycline therapy in multiple-resistant Klebsiella pneumoniae.Annals of clinical microbiology and antimicrobials · 2025Article
- In vitro activity of Eravacycline against carbapenem-resistant gram-negative bacilli and associated risk factors for non-susceptible infections from a tertiary hospital in fujian, China from 2021 to 2024.BMC microbiology · 2025Article
- Genomic insights into tigecycline non-susceptibility in Clostridioides difficile: the role of the Tet P determinant and efflux mechanisms.BMC microbiology · 2025Article
- EPS inhibitor treatment of Salmonella impacts evolution without selecting for resistance to biofilm inhibition.NPJ biofilms and microbiomes · 2025Article
- Article
- Phenotypic Profiling of Tigecycline-resistant Klebsiella pneumoniae Strains Induced In vitro.Current microbiology · 2024Article
- Mechanisms of tigecycline resistance in Gram-negative bacteria: A narrative review.Engineering microbiology · 2024Review
- Occurrence and mechanisms of tigecycline resistance in carbapenem- and colistin-resistant Klebsiella pneumoniae in Thailand.Scientific reports · 2024Article
- The tigecycline resistance mechanisms in Gram-negative bacilli.Frontiers in cellular and infection microbiology · 2024Review
- Characterization of two multidrug-resistantFrontiers in microbiology · 2023Article
- Development of Resistance to Eravacycline by Klebsiella pneumoniae and Collateral Sensitivity-Guided Design of Combination Therapies.Microbiology spectrum · 2022Article
- ISMicrobial genomics · 2022Article
- Targeting the Holy Triangle of Quorum Sensing, Biofilm Formation, and Antibiotic Resistance in Pathogenic Bacteria.Microorganisms · 2022Review
- Phenotypic and Genotypic Characterization of a Hypervirulent Carbapenem-Resistant Klebsiella pneumoniae ST17-KL38 Clinical Isolate Harboring the Carbapenemase IMP-4.Microbiology spectrum · 2022Article
- Dissemination and prevalence of plasmid-mediated high-level tigecycline resistance geneFrontiers in microbiology · 2022Review
- Resistance evolution of hypervirulent carbapenem-resistantEmerging microbes & infections · 2021Article
- Molecular characterization of carbapenem-resistantJournal of medical microbiology · 2021Article
- Acquisition of Tigecycline Resistance by Carbapenem-ResistantFrontiers in microbiology · 2021Article
- Effects of Ribosomal Protein S10 Flexible Loop Mutations on Tetracycline and Tigecycline Susceptibility ofFrontiers in microbiology · 2021Article
- Characterization of Tigecycline-HeteroresistantFrontiers in microbiology · 2021Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Klebsiella pneumoniae is a gram-negative bacterium that causes numerous diseases, including pneumonia and urinary tract infections. An increase in multidrug resistance has complicated the treatment of these bacterial infections, and although tigecycline shows activity against a broad spectrum of bacteria, resistant strains have emerged. In this study, the whole genomes of two clinical and six laboratory-evolved strains were sequenced to identify putative mutations related to tigecycline resistance. Of seven tigecycline-resistant strains, seven (100%) had ramR mutations, five (71.4%) had lon mutations, one (14.2%) had a ramA mutation, and one (14.2%) had an rpsJ mutation. A higher fitness cost was observed in the laboratory-evolved strains but not in the clinical strains. A transcriptome analysis demonstrated high expression of the ramR operon and acrA in all tigecycline-resistant strains. Genes involved in nitrogen metabolism were induced in the laboratory-evolved strains compared with the wild-type and clinical strains, and this difference in nitrogen metabolism reflected the variation between the laboratory-evolved and the clinical strains. Complementation experiments showed that both the wild-type ramR and the lon genes could partially restore the tigecycline sensitivity of K. pneumoniae. We believe that this manuscript describes the first construct of a lon mutant in K. pneumoniae, which allowed confirmation of its association with tigecycline resistance. Our findings illustrate the importance of the ramR operon and the lon and rpsJ genes in K. pneumoniae resistance to tigecycline.
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