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@ARTICLE{Hoernke:638020,
      author       = {Hoernke, Maria and Shi, Shuai and Hubbard, Alasdair T. M.
                      and Geringer, Nina and Strati, Fabio and Shen, Chen and
                      Wölk, Christian and Harvey, Richard D.},
      title        = {{D}aptomycin membrane activity is modulated by the
                      localized interplay between calcium ions and phospholipids
                      in monolayers and bilayers containing a
                      lysyl-phosphatidylglycerol analogue},
      journal      = {Biochimica et biophysica acta / Biomembranes},
      volume       = {1867},
      number       = {8},
      issn         = {0005-2728},
      address      = {Amsterdam},
      publisher    = {Elsevier},
      reportid     = {PUBDB-2025-03968},
      pages        = {184452},
      year         = {2025},
      abstract     = {Using the stable synthetic analogue
                      3-aza-dehydroxylysyl-phosphatidylglycerol (3adLPG), the
                      putative role of native staphylococcal LPG in inhibiting the
                      antibiotic daptomycin from binding to its target
                      phosphatidylglycerol (PG), was investigated with respect to
                      interfacial interactions between these lipids, daptomycin,
                      and calcium ions. The influence of lipid monolayer/bilayer
                      composition and interfacial ion concentrations upon the
                      structure and integrity of model membranes were probed after
                      daptomycin challenge using a combination of surface x-ray
                      scattering techniques and fluorescence assays. In models
                      representing the membrane composition of the daptomycin
                      susceptible phenotype consisting of PG/3adLPG in a 7:3 M
                      ratio, calcium ions drive the formation of two separate
                      phases; Ca2+ cross-linked PG/PG pairs and PG/3adLPG ion
                      pairs. Daptomycin is able to bind directly to the lipids in
                      the PG/PG phase and increases the amount of interfacial Ca2+
                      ions to a level sufficient to displace 3adLPG from ion pairs
                      with PG, and thus binds to its target PG. In bilayers with
                      mixed chain lipids, daptomycin leads to pronounced membrane
                      perturbations and enhanced permeability. Sequestering all of
                      the available PG into PG/3adLPG ion pairs, therefore, would
                      represent a putative daptomycin non-susceptible membrane.
                      Daptomycin binding and the extent of subsequent lipid
                      structural changes are reduced in these membranes. This
                      implies that in bacteria, native LPG biosynthesis would need
                      to ensure either an equivalence or an excess in relation to
                      membrane PG content, in order for this mechanism alone to
                      significantly contribute to daptomycin resistance.},
      cin          = {DOOR ; HAS-User / FS-PET-D},
      ddc          = {570},
      cid          = {I:(DE-H253)HAS-User-20120731 /
                      I:(DE-H253)FS-PET-D-20190712},
      pnm          = {633 - Life Sciences – Building Blocks of Life: Structure
                      and Function (POF4-633) / FS-Proposal: I-20190426
                      (I-20190426) / DFG project G:(GEPRIS)415894560 -
                      Polymer-induzierte endosomale Freisetzung für drug
                      delivery: die mechanistische Verknüpfung von pH-induzierter
                      Polymerbindung, Leakage, Fusion und anderem
                      physikalisch-chemischen Membranverhalten (415894560) / 6G3 -
                      PETRA III (DESY) (POF4-6G3)},
      pid          = {G:(DE-HGF)POF4-633 / G:(DE-H253)I-20190426 /
                      G:(GEPRIS)415894560 / G:(DE-HGF)POF4-6G3},
      experiment   = {EXP:(DE-H253)P-P08-20150101},
      typ          = {PUB:(DE-HGF)16},
      doi          = {10.1016/j.bbamem.2025.184452},
      url          = {https://bib-pubdb1.desy.de/record/638020},
}