ArticleAntimicrobial agents and chemotherapy2012
Identification of hopanoid biosynthesis genes involved in polymyxin resistance in Burkholderia multivorans.
Article in Antimicrobial agents and chemotherapy, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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33 citing papers in PubMed, 61 citations in OpenAlex.
- Pulmonary microbial spectrum ofFrontiers in medicine · 2025Article
- Molecular Mechanisms of Bacterial Resistance to Antimicrobial Peptides in the Modern Era: An Updated Review.Microorganisms · 2024Review
- Hopanoid lipids promote soybeanmBio · 2024Article
- Profiling cell envelope-antibiotic interactions reveals vulnerabilities to β-lactams in a multidrug-resistant bacterium.Nature communications · 2023Article
- Complete sequences of conjugal helper plasmids pRK2013 and pEVS104.microPublication biology · 2023Article
- 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
- Combining Colistin and Fluconazole Synergistically Increases Fungal Membrane Permeability and Antifungal Cidality.ACS infectious diseases · 2021Article
- The LactococcalInternational journal of molecular sciences · 2021Article
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- Loss ofmSphere · 2019Article
- An Approach to Measuring Colistin Plasma Levels Regarding the Treatment of Multidrug-Resistant Bacterial Infection.Antibiotics (Basel, Switzerland) · 2019Review
- An Inward-Rectifier Potassium Channel Coordinates the Properties of Biologically Derived Membranes.Biophysical journal · 2019Article
- A DedA Family Membrane Protein Is Required forFrontiers in microbiology · 2019Article
- Lipid Phases and Cell Geometry During the Cell Cycle ofFrontiers in microbiology · 2019Article
- Targeting the Nonmevalonate Pathway in Burkholderia cenocepacia Increases Susceptibility to Certain β-Lactam Antibiotics.Antimicrobial agents and chemotherapy · 2018Article
- Integrated roles of BclA and DD-carboxypeptidase 1 in Bradyrhizobium differentiation within NCR-producing and NCR-lacking root nodules.Scientific reports · 2017Article
- Crystal structures of theProceedings of the National Academy of Sciences of the United States of America · 2017Article
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4 authors at 1 institution in 1 country.
Funding
Abstract
A major challenge to clinical therapy of Burkholderia cepacia complex (Bcc) pulmonary infections is their innate resistance to a broad range of antimicrobials, including polycationic agents such as aminoglycosides, polymyxins, and cationic peptides. To identify genetic loci associated with this phenotype, a transposon mutant library was constructed in B. multivorans ATCC 17616 and screened for increased susceptibility to polymyxin B. Compared to the parent strain, mutant 26D7 exhibited 8- and 16-fold increases in susceptibility to polymyxin B and colistin, respectively. Genetic analysis of mutant 26D7 indicated that the transposon inserted into open reading frame (ORF) Bmul_2133, part of a putative hopanoid biosynthesis gene cluster. A strain with a mutation in another ORF in this cluster, Bmul_2134, was constructed and named RMI19. Mutant RMI19 also had increased polymyxin susceptibility. Hopanoids are analogues of eukaryotic sterols involved in membrane stability and barrier function. Strains with mutations in Bmul_2133 and Bmul_2134 showed increased permeability to 1-N-phenylnaphthylamine in the presence of increasing concentrations of polymyxin, suggesting that the putative hopanoid biosynthesis genes are involved in stabilizing outer membrane permeability, contributing to polymyxin resistance. Results from a dansyl-polymyxin binding assay demonstrated that polymyxin B does not bind well to the parent or mutant strains, suggesting that Bmul_2133 and Bmul_2134 contribute to polymyxin B resistance by a mechanism that is independent of lipopolysaccharide (LPS) binding. Through this work, we propose a role for hopanoid biosynthesis as part of the multiple antimicrobial resistance phenotype in Bcc bacteria.
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