ArticlemBio2021
OXA-23 β-Lactamase Overexpression in Acinetobacter baumannii Drives Physiological Changes Resulting in New Genetic Vulnerabilities.
Article in mBio, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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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
25 citing papers in PubMed, 30 citations in OpenAlex.
- A monoclonal antibody targeting OXA23 restores carbapenem susceptibility in global epidemic carbapenem-resistantAntimicrobial agents and chemotherapy · 2026Article
- Multiply Perturbed Response: A Computational Protocol to Identify Cooperative Allosteric Residue Combinations Driving Protein Conformational Transitions.Bio-protocol · 2026Article
- Leveraging the lipoprotein trafficking pathway for the development of novel antimicrobials.RSC chemical biology · 2026Review
- A conserved hub protein required for peptidoglycan remodeling and cell division inProceedings of the National Academy of Sciences of the United States of America · 2025Article
- The lipoprotein biosynthesis pathway: key to OXA-mediated carbapenem resistance inAntimicrobial agents and chemotherapy · 2025Article
- Subinhibitory Concentrations of Oxacillin Alter Motility, Biofilm Production, and Transformation Capability of the Oxacillinase-Producing Acinetobacter baumannii.Current microbiology · 2025Article
- Insights into the Metabolic Adaptations of a Carbapenem-ResistantInternational journal of molecular sciences · 2025Article
- Repurposing a drug to punish carbapenem-resistantProceedings of the National Academy of Sciences of the United States of America · 2025Article
- OXA β-lactamases frommBio · 2025Article
- Integrative review on Acinetobacter baumannii as a multidrug-resistant pathogen: resistance mechanisms and therapeutic perspectives in the context of nosocomial infections.Revista da Sociedade Brasileira de Medicina Tropical · 2025Review
- OXA β-lactamases frombioRxiv : the preprint server for biology · 2024Article
- A single-center analysis of clonal transmission of carbapenem-resistant Acinetobacter baumannii among intensive care unit patients during the COVID-19 pandemic.Scientific reports · 2024Article
- Antibiotic Resistance in the Elderly: Mechanisms, Risk Factors, and Solutions.Microorganisms · 2024Review
- A series of vectors for inducible gene expression in multidrug-resistantApplied and environmental microbiology · 2024Article
- Clinical and microbiological features of a cohort of patients with Acinetobacter baumannii bloodstream infections.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2024Article
- Structural and Dynamic Features of Acinetobacter baumannii OXA-66 β-Lactamase Explain Its Stability and Evolution of Novel Variants.Journal of molecular biology · 2024Article
- Costs of antibiotic resistance genes depend on host strain and environment and can influence community composition.Proceedings. Biological sciences · 2024Article
- Seasonal meropenem resistance in Acinetobacter baumannii and influence of temperature-driven adaptation.BMC microbiology · 2024Article
- Drug Discovery in the Field of β-Lactams: An Academic Perspective.Antibiotics (Basel, Switzerland) · 2024Review
- Evaluation of Antibiotic Resistance Mechanisms in Gram-Negative Bacteria.Antibiotics (Basel, Switzerland) · 2023Review
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 2 countries.
Funding
Abstract
β-Lactamase expression is the major mechanism of resistance to penicillins, cephalosporins, and carbapenems in the multidrug-resistant (MDR) bacterium Acinetobacter baumannii. In fact, stable high-level expression of at least one β-lactamase has been rapidly increasing and reported to occur in up to 98.5% of modern A. baumannii isolates recovered in the clinic. Moreover, the OXA-51 β-lactamase is universally present in the A. baumannii chromosome, suggesting it may have a cellular function beyond antibiotic resistance. However, the consequences associated with OXA β-lactamase overexpression on A. baumannii physiology are not well understood. Using peptidoglycan composition analysis, we show that overexpressing the OXA-23 β-lactamase in A. baumannii drives significant collateral changes with alterations consistent with increased amidase activity. Consequently, we predicted that these changes create new cellular vulnerabilities. As proof of principle, a small screen of random transposon insertions revealed three genes, where mutations resulted in a greater than 19-fold loss of viability when OXA-23 was overexpressed. The identified genes remained conditionally essential even when a catalytically inactive OXA-23 β-lactamase was overexpressed. In addition, we demonstrated a synergistic lethal relationship between OXA-23 overexpression and a CRISPR interference (CRISPRi) knockdown of the essential peptidoglycan synthesis enzyme MurA. Last, OXA-23 overexpression sensitized cells to two inhibitors of peptidoglycan synthesis, d-cycloserine and fosfomycin. Our results highlight the impact of OXA-23 hyperexpression on peptidoglycan integrity and reveal new genetic vulnerabilities, which may represent novel targets for antimicrobial agents specific to MDR A. baumannii and other OXA β-lactamase-overexpressing
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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.