Trial reportProceedings of the National Academy of Sciences of the United States of America2013
Enhanced in vivo fitness of carbapenem-resistant oprD mutants of Pseudomonas aeruginosa revealed through high-throughput sequencing.
Trial report in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers.
What it found
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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.
The trial behind it
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
81 citing papers in PubMed, 141 citations in OpenAlex.
- Comparison ofInfection and immunity · 2026Article
- A periplasmic metallochaperone (PmcY) couples ZnAntimicrobial agents and chemotherapy · 2026Article
- Carbapenem-resistance oprD mutations reshape Pseudomonas aeruginosa host-pathogen interactions during infection.Nature communications · 2026Article
- Overexpression of Escherichia coli yaiX Confers Multidrug Resistance and Enhances Virulence in the Silkworm Infection Model.Microbiology and immunology · 2026Article
- Comparison ofbioRxiv : the preprint server for biology · 2026Article
- Introducing gold-standard essential gene datasets for Pseudomonas aeruginosa to enhance Tn-Seq analyses.PLoS computational biology · 2026Article
- Molecular epidemiological association between antimicrobial resistance characteristics and type III secretion system in carbapenem-resistantFrontiers in cellular and infection microbiology · 2026Article
- Role of R5 pyocin in the predominance of high-risk Pseudomonas aeruginosa isolates.Microbiological research · 2025Article
- Global analysis of the Hfq-mediated RNA interactome discovers a MicA homolog that affects the cytotoxicity, biofilm formation, and resistance to complement of Bordetella pertussis.Nucleic acids research · 2025Article
- Evolutionary rescue of sphericaleLife · 2025Article
- Article
- Interplay between porin deficiency, fitness, and virulence in carbapenem-non-susceptible Pseudomonas aeruginosa and Enterobacteriaceae.PLoS pathogens · 2025Review
- The OprF porin as a potential target for the restoration of carbapenem susceptibility inAntimicrobial agents and chemotherapy · 2024Article
- Impact of multidrug resistance on the virulence and fitness of Pseudomonas aeruginosa: a microbiological and clinical perspective.Infection · 2024Review
- Advances in Development of Novel Therapeutic Strategies against Multi-Drug ResistantAntibiotics (Basel, Switzerland) · 2024Review
- Effect ofFrontiers in microbiology · 2024Article
- Development of an antibody fused with an antimicrobial peptide targeting Pseudomonas aeruginosa: A new approach to prevent and treat bacterial infections.PLoS pathogens · 2023Article
- Age of Antibiotic Resistance in MDR/XDR Clinical Pathogen ofPharmaceuticals (Basel, Switzerland) · 2023Review
- A high-throughput sequencing approach identifies immunotherapeutic targets for bacterial meningitis in neonates.EBioMedicine · 2023Article
- The balance between antibiotic resistance and fitness/virulence inFrontiers in microbiology · 2023Review
21 more citing papers are in PubMed but not listed here.
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Authors and funding
16 authors at 4 institutions in 2 countries.
Funding
Abstract
An important question regarding the biologic implications of antibiotic-resistant microbes is how resistance impacts the organism's overall fitness and virulence. Currently it is generally thought that antibiotic resistance carries a fitness cost and reduces virulence. For the human pathogen Pseudomonas aeruginosa, treatment with carbapenem antibiotics is a mainstay of therapy that can lead to the emergence of resistance, often through the loss of the carbapenem entry channel OprD. Transposon insertion-site sequencing was used to analyze the fitness of 300,000 mutants of P. aeruginosa strain PA14 in a mouse model for gut colonization and systemic dissemination after induction of neutropenia. Transposon insertions in the oprD gene led not only to carbapenem resistance but also to a dramatic increase in mucosal colonization and dissemination to the spleen. These findings were confirmed in vivo with different oprD mutants of PA14 as well as with related pairs of carbapenem-susceptible and -resistant clinical isolates. Compared with OprD(+) strains, those lacking OprD were more resistant to killing by acidic pH or normal human serum and had increased cytotoxicity against murine macrophages. RNA-sequencing analysis revealed that an oprD mutant showed dramatic changes in the transcription of genes that may contribute to the various phenotypic changes observed. The association between carbapenem resistance and enhanced survival of P. aeruginosa in infected murine hosts suggests that either drug resistance or host colonization can cause the emergence of more pathogenic, drug-resistant P. aeruginosa clones in a single genetic event.
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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.