ArticleJournal of bacteriology2010
Emergence of Pseudomonas aeruginosa strains producing high levels of persister cells in patients with cystic fibrosis.
Article in Journal of bacteriology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 336 papers.
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Who cites it
336 citing papers in PubMed, 624 citations in OpenAlex.
- Heteroresistance tolerance and persistence in antibiotic treatment failure.Folia microbiologica · 2026Review
- Proteomic Analysis of Three Independent Series of Sequential Cystic Fibrosis Strains in an International Pseudomonas aeruginosa Reference Panel Indicates Positive Selection in Late Infection Strains.MicrobiologyOpen · 2026Article
- Seeing Bacterial Persistence Through Different Experimental Lenses: How Methodology Shapes Biological Interpretation.Pathogens (Basel, Switzerland) · 2026Review
- Contributions of persisters and the Eagle effect to survival ofMicrobiology spectrum · 2026Article
- Lipopolysaccharide insertion and vesicle mediated turnover drive growth independent outer membrane adaptation in Escherichia coli.Nature communications · 2026Article
- Mechanism of persister formation in response to nitrogen starvation.Nature communications · 2026Article
- Beyond Resistance Genes:Life (Basel, Switzerland) · 2026Review
- Antibiotic resistance mechanisms and global resistance patterns of Pseudomonas aeruginosa in microbial keratitis.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2026Review
- Antibiotic exposure and recovery of persister states influence virulence phenotypes in Pseudomonas aeruginosa.Archives of microbiology · 2026Article
- Antimicrobial Effect of Spices and Their Phytochemicals: A Novel Approach to Overcoming Antibiotic Resistance.MedComm · 2026Review
- Article
- Beyond Resistance: Phenotypic Plasticity in Bacterial Responses to Antibiotics, Oxidative Stress and Antimicrobial Photodynamic Inactivation.Molecules (Basel, Switzerland) · 2026Review
- Large-scale testing of antimicrobial lethality at single-cell resolution predicts mycobacterial infection outcomes.Nature microbiology · 2026Article
- Phage-Based Approaches to ChronicAntibiotics (Basel, Switzerland) · 2026Review
- Microenvironmental effects of a non-antibiotic therapy for a chronic Polymicrobial infection Alter microbial physiology, competition, and virulence.The ISME journal · 2026Article
- Safety Assessment ofJournal of toxicology · 2026Article
- Regulatory time-kill sequencing maps antibiotic-specific transcriptional control ofFrontiers in microbiology · 2026Article
- A broad-host-range inhalable phage cocktail for treatment of multidrug-resistantFrontiers in cellular and infection microbiology · 2026Article
- Molecular Basis of Persister Awakening and Lag-Phase Recovery inInternational journal of molecular sciences · 2026Review
- Friend or foe: the gut microbiota as a modulator of disease trajectory in trauma, surgery, and critical illness.Gut microbes · 2025Review
276 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
The majority of cystic fibrosis (CF) patients succumb to a chronic infection of the airway with Pseudomonas aeruginosa. Paradoxically, pathogenic strains are often susceptible to antibiotics, but the infection cannot be eradicated with antimicrobial therapy. We find that in a majority of patients with airway infections, late isolates of P. aeruginosa produce increased levels of drug-tolerant persister cells. The genomes of a clonal pair of early/late isolates from a single patient have been previously sequenced, and the late isolate (obtained at age 96 months) showed a 100-fold increase in persister levels. The 96-month isolate carries a large number of mutations, including a mutation in mutS that confers a hypermutator phenotype. There is also a mutation in the mexZ repressor controlling the expression of the MexXY-OprM multidrug pump, which results in a moderate increase in the ofloxacin, carbenicillin, and tobramycin MICs. Knocking out the mexXY locus restored the resistance to that of the parent strain but did not affect the high levels of persisters formed by the 96-month isolate. This suggests that the late isolate is a high-persister (hip) mutant. Increased persister formation was observed in exponential phase, stationary phase, and biofilm populations of the 96-month isolate. Analysis of late isolates from 14 additional patients indicated that 10 of them are hip mutants. Most of these hip mutants did not have higher drug resistance. Increased persister formation appears to be their sole mechanism for surviving chemotherapy. Taken together, these findings suggest a link between persisters and recalcitrance of CF infection and identify an overlooked culprit-high-persister mutants producing elevated levels of drug-tolerant cells. Persisters may play a similarly critical role in the recalcitrance of other chronic infections.
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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.