ArticleAntimicrobial agents and chemotherapy2014
IS5 element integration, a novel mechanism for rapid in vivo emergence of tigecycline nonsusceptibility in Klebsiella pneumoniae.
Article in Antimicrobial agents and chemotherapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 56 citations in OpenAlex.
- A review on hypervirulent and multidrug-resistant Klebsiella pneumoniae: An emerging threat to human health.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- Emergence and genomic characterization of hypervirulent ST23/K1Frontiers in microbiology · 2026Article
- RND/HAE-1 members in the Pseudomonadota phylum: exploring multidrug resistance.Biophysical reviews · 2025Review
- Review
- Mechanisms of tigecycline resistance in Gram-negative bacteria: A narrative review.Engineering microbiology · 2024Review
- Article
- Plant-Origin Components: New Players to Combat Antibiotic Resistance inInternational journal of molecular sciences · 2024Review
- The tigecycline resistance mechanisms in Gram-negative bacilli.Frontiers in cellular and infection microbiology · 2024Review
- Insights into Kinases of ESKAPE Pathogens for Therapeutic Interventions.Cardiovascular & hematological agents in medicinal chemistry · 2024Review
- Characteristics of antibiotic resistance mechanisms and genes ofOpen medicine (Warsaw, Poland) · 2023Review
- Review
- Article
- Tigecycline antibacterial activity, clinical effectiveness, and mechanisms and epidemiology of resistance: narrative review.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2022Review
- Targeting the Holy Triangle of Quorum Sensing, Biofilm Formation, and Antibiotic Resistance in Pathogenic Bacteria.Microorganisms · 2022Review
- Performance of VITEK 2, E-test, Kirby-Bauer disk diffusion, and modified Kirby-Bauer disk diffusion compared to reference broth microdilution for testing tigecycline susceptibility of carbapenem-resistant K. pneumoniae and A. baumannii in a multicenter study in China.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2021Article
- Common Adaptive Strategies Underlie Within-Host Evolution of Bacterial Pathogens.Molecular biology and evolution · 2021Article
- Acquisition of Tigecycline Resistance by Carbapenem-ResistantFrontiers in microbiology · 2021Article
- CusS-CusR Two-Component System Mediates Tigecycline Resistance in Carbapenem-ResistantFrontiers in microbiology · 2019Article
- Insertion element mediatedInfection and drug resistance · 2018Article
- The Rapid Emergence of Tigecycline Resistance inFrontiers in microbiology · 2018Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tigecycline nonsusceptibility is concerning because tigecycline is increasingly relied upon to treat carbapenem- or colistin-resistant organisms. In Enterobacteriaceae, tigecycline nonsusceptibility is mediated by the AcrAB-TolC efflux pump, among others, and pump activity is often a downstream effect of mutations in their transcriptional regulators, cognate repressor genes, or noncoding regions, as demonstrated in Enterobacteriaceae and Acinetobacter isolates. Here, we report the emergence of tigecycline nonsusceptibility in a longitudinal series of multidrug-resistant (MDR) and extensively drug-resistant (XDR) Klebsiella pneumoniae isolates collected during tigecycline therapy and the elucidation of its resistance mechanisms. Clinical isolates were recovered prior to and during tigecycline therapy of a 2.5-month-old Honduran neonate. Antimicrobial susceptibility tests to tigecycline determined that the MIC increased from 1 to 4 μg/ml prior to the completion of tigecycline therapy. Unlike other studies, we did not find increased expression of ramA, ramR, oqxA, acrB, marA, or rarA genes by reverse transcription-quantitative PCR (qRT-PCR). Whole-genome sequencing revealed an IS5 insertion element in nonsusceptible isolates 85 bp upstream of a putative efflux pump operon, here named kpgABC, previously unknown to be involved in resistance. Introduction of the kpgABC genes in a non-kpgABC background increased the MIC of tigecycline 4-fold and is independent of a functional AcrAB-TolC pump. This is the first report to propose a function for kpgABC and identify an insertion element whose presence correlated with the in vivo development of tigecycline nonsusceptibility in K. pneumoniae.
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