ArticleThe Journal of antimicrobial chemotherapy2015
The transcriptomic response of Acinetobacter baumannii to colistin and doripenem alone and in combination in an in vitro pharmacokinetics/pharmacodynamics model.
Article in The Journal of antimicrobial chemotherapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed, 82 citations in OpenAlex.
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- Transcriptomic investigations of polymyxins and colistin/sulbactam combination against carbapenem-resistantComputational and structural biotechnology journal · 2024Article
- Microbiome-derived antimicrobial peptides show therapeutic activity against the critically important priority pathogen, Acinetobacter baumannii.NPJ biofilms and microbiomes · 2024Article
- Bisphenol S Promotes the Transfer of Antibiotic Resistance Genes via Transformation.International journal of molecular sciences · 2024Article
- Deciphering Antibiotic-Targeted Metabolic Pathways inLife (Basel, Switzerland) · 2024Article
- Structural and functional characterization of FabG4 from Mycolicibacterium smegmatis.Acta crystallographica. Section F, Structural biology communications · 2024Article
- Sub-inhibitory concentrations of colistin and imipenem impact the expression of biofilm-associated genes in Acinetobacter baumannii.Archives of microbiology · 2024Article
- Unveiling the role of BON domain-containing proteins in antibiotic resistance.Frontiers in microbiology · 2024Review
- Understanding Antimicrobial Resistance Using Genome-Scale Metabolic Modeling.Antibiotics (Basel, Switzerland) · 2023Review
- The RND Efflux Pump Gene Expression in the Biofilm Formation ofAntibiotics (Basel, Switzerland) · 2023Article
- Role of efflux pumps, their inhibitors, and regulators in colistin resistance.Frontiers in microbiology · 2023Review
- Article
- Caulobacter lipid A is conditionally dispensable in the absence of fur and in the presence of anionic sphingolipids.Cell reports · 2022Article
- Whole-Genome Sequencing of a Colistin-ResistantAntibiotics (Basel, Switzerland) · 2022Article
- Correlative proteomics identify the key roles of stress tolerance strategies in Acinetobacter baumannii in response to polymyxin and human macrophages.PLoS pathogens · 2022Article
- Artificial sweeteners stimulate horizontal transfer of extracellular antibiotic resistance genes through natural transformation.The ISME journal · 2022Article
- Genome diversity of domesticatedMicrobial genomics · 2022Article
- Pathway Driven Target Selection inFrontiers in cellular and infection microbiology · 2022Article
- Polymyxin B1 within theBiophysical reviews · 2021Review
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectivesColistin remains a last-line treatment for MDR Acinetobacter baumannii and combined use of colistin and carbapenems has shown synergistic effects against MDR strains. In order to understand the bacterial responses to these antibiotics, we analysed the transcriptome of A. baumannii following exposure to each.
methodsRNA sequencing was employed to determine changes in the transcriptome following treatment with colistin and doripenem, both alone and in combination, using an in vitro pharmacokinetics (PK)/pharmacodynamics model to mimic the PK of both antibiotics in patients.
resultsAfter treatment with colistin (continuous infusion at 2 mg/L), >400 differentially regulated genes were identified, including many associated with outer membrane biogenesis, fatty acid metabolism and phospholipid trafficking. No genes were differentially expressed following treatment with doripenem (Cmax 25 mg/L, t1/2 1.5 h) for 15 min, but 45 genes were identified as differentially expressed after 1 h of growth under this condition. Treatment of A. baumannii with both colistin and doripenem together for 1 h resulted in >450 genes being identified as differentially expressed. More than 70% of these gene expression changes were also observed following colistin treatment alone.
conclusionsThese data suggest that colistin causes gross damage to the outer membrane, facilitates lipid exchange between the inner and outer membrane and alters the normal asymmetric outer membrane composition. The transcriptional response to colistin was highly similar to that observed for an LPS-deficient strain, indicating that many of the observed changes are responses to outer membrane instability resulting from LPS loss.
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