ArticleAntimicrobial agents and chemotherapy2014
Fosmidomycin decreases membrane hopanoids and potentiates the effects of colistin on Burkholderia multivorans clinical isolates.
Article in Antimicrobial agents and chemotherapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16 citing papers in PubMed, 33 citations in OpenAlex.
- Construction of a Bacterial Lipidomics Analytical Platform: Pilot Validation with Bovine Paratuberculosis Serum.Metabolites · 2023Article
- Over 40 Years of Fosmidomycin Drug Research: A Comprehensive Review and Future Opportunities.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Next-Generation Polymyxin Class of Antibiotics: A Ray of Hope Illuminating a Dark Road.Antibiotics (Basel, Switzerland) · 2022Review
- Lipid Transport Across Bacterial Membranes.Annual review of cell and developmental biology · 2022Review
- Spectroscopic signatures of bilayer ordering in native biological membranes.Biochimica et biophysica acta. Biomembranes · 2022Article
- Structural and Functional Diversity of Resistance-Nodulation-Cell Division Transporters.Chemical reviews · 2021Review
- The LactococcalInternational journal of molecular sciences · 2021Article
- The antimicrobial peptide Polybia-MP1 differentiates membranes with the hopanoid, diplopterol from those with cholesterol.BBA advances · 2021Article
- An Inward-Rectifier Potassium Channel Coordinates the Properties of Biologically Derived Membranes.Biophysical journal · 2019Article
- Targeting the Nonmevalonate Pathway in Burkholderia cenocepacia Increases Susceptibility to Certain β-Lactam Antibiotics.Antimicrobial agents and chemotherapy · 2018Article
- Crystal structures of theProceedings of the National Academy of Sciences of the United States of America · 2017Article
- Hopanoid-free Methylobacterium extorquens DM4 overproduces carotenoids and has widespread growth impairment.PloS one · 2017Article
- Antibiotic resistance in Burkholderia species.Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy · 2016Review
- Hopanoids as functional analogues of cholesterol in bacterial membranes.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Quantitative hopanoid analysis enables robust pattern detection and comparison between laboratories.Geobiology · 2015Article
- Methylation at the C-2 position of hopanoids increases rigidity in native bacterial membranes.eLife · 2015Article
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Burkholderia cepacia complex (Bcc) pulmonary infections in people living with cystic fibrosis (CF) are difficult to treat because of the extreme intrinsic resistance of most isolates to a broad range of antimicrobials. Fosmidomycin is an antibacterial and antiparasitic agent that disrupts the isoprenoid biosynthesis pathway, a precursor to hopanoid biosynthesis. Hopanoids are involved in membrane stability and contribute to polymyxin resistance in Bcc bacteria. Checkerboard MIC assays determined that although isolates of the Bcc species B. multivorans were highly resistant to treatment with fosmidomycin or colistin (polymyxin E), antimicrobial synergy was observed in certain isolates when the antimicrobials were used in combination. Treatment with fosmidomycin decreased the MIC of colistin for isolates as much as 64-fold to as low as 8 μg/ml, a concentration achievable with colistin inhalation therapy. A liquid chromatography-tandem mass spectrometry technique was developed for the accurate quantitative determination of underivatized hopanoids in total lipid extracts, and bacteriohopanetetrol cyclitol ether (BHT-CE) was found to be the dominant hopanoid made by B. multivorans. The amount of BHT-CE made was significantly reduced upon fosmidomycin treatment of the bacteria. Uptake assays with 1-N-phenylnaphthylamine were used to determine that dual treatment with fosmidomycin and colistin increases membrane permeability, while binding assays with boron-dipyrromethene-conjugated polymyxin B illustrated that the addition of fosmidomycin had no impact on polymyxin binding. This work indicates that pharmacological suppression of membrane hopanoids with fosmidomycin treatment can increase the susceptibility of certain clinical B. multivorans isolates to colistin, an agent currently in use to treat pulmonary infections in CF patients.
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