ArticleNature microbiology2016
Antibiotic failure mediated by a resistant subpopulation in Enterobacter cloacae.
Article in Nature microbiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 156 papers, 1 of them a synthesis that pooled it.
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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.
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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.
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Who cites it
156 citing papers in PubMed, 1 synthesis or guideline pooled it, 242 citations in OpenAlex.
- Global trends and research profile of antibiotic heteroresistance: a bibliometric and visual analysis.Frontiers in microbiology · 2026Pooled it
- Rapid Detection of Methicillin-Resistant Staphylococcus aureus in BAL: A Pilot Randomized Controlled Trial.Chest · 2019Trial
- Natural molecule potentiates colistin efficacyVirulence · 2026Article
- Dual resistance to carbapenems and colistin inEmerging microbes & infections · 2026Article
- Heteroresistance tolerance and persistence in antibiotic treatment failure.Folia microbiologica · 2026Review
- Combinatorial action of regulatory systems generates colistin heteroresistance.Science advances · 2026Article
- Heterogeneity in the response to the metabolic environment drives fosfomycin heteroresistance.Nature communications · 2026Article
- High prevalence of colistin heteroresistance in Pseudomonas aeruginosa bloodstream isolates and associated clinical factors.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2026Article
- Bacterial heteroresistance mechanisms, dynamics, and emerging diagnostic approaches.Bioscience reports · 2026Review
- Biofilm Formation and the Pore ProteinsAntibiotics (Basel, Switzerland) · 2026Article
- Heterogeneity in microbial antibiotic responses: genetic basis and within-host evolution.Trends in genetics : TIG · 2026Review
- Beyond minimum inhibitory concentration values: clinical and diagnostic challenges of colistin heteroresistance in Acinetobacter baumannii.Molecular biology reports · 2026Review
- Multiplexed, rapid phenotypic antibiotic susceptibility testing based on angle-resolved light scattering imaging of microfluidic droplets.Journal of advanced research · 2026Article
- Tandem amplification of theMicrobiology spectrum · 2026Article
- Heteroresistance to amikacin inMicrobiology spectrum · 2026Article
- Evaluation of a simplified agar-based population analysis profiling as a practical alternative for detecting heteroresistance in clinical bacterial isolates.BMC infectious diseases · 2026Article
- High-resolution, high-throughput detection of hidden antibiotic resistance with the dilution-and-delay (DnD) susceptibility assay.Nature communications · 2026Article
- Translocation of bacteria from the gut to the brain in mice.PLoS biology · 2026Article
- An Investigation of Colistin Heteroresistance inBioMed research international · 2026Article
- Study on the heteroresistance of carbapenem-resistant Klebsiella pneumoniae to Tigecycline and Polymyxin B and antibacterial activity of combined drugs in vitro.BMC microbiology · 2025Article
96 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 5 institutions in 1 country.
Funding
Abstract
Antibiotic resistance is a major public health threat, further complicated by unexplained treatment failures caused by bacteria that appear antibiotic susceptible. We describe an Enterobacter cloacae isolate harbouring a minor subpopulation that is highly resistant to the last-line antibiotic colistin. This subpopulation was distinct from persisters, became predominant in colistin, returned to baseline after colistin removal and was dependent on the histidine kinase PhoQ. During murine infection, but in the absence of colistin, innate immune defences led to an increased frequency of the resistant subpopulation, leading to inefficacy of subsequent colistin therapy. An isolate with a lower-frequency colistin-resistant subpopulation similarly caused treatment failure but was misclassified as susceptible by current diagnostics once cultured outside the host. These data demonstrate the ability of low-frequency bacterial subpopulations to contribute to clinically relevant antibiotic resistance, elucidating an enigmatic cause of antibiotic treatment failure and highlighting the critical need for more sensitive diagnostics.
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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.