{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T14:53:28Z","timestamp":1791298408264,"version":"4.1.0"},"posted":{"date-parts":[[2026,6,25]]},"group-title":"Biophysics","reference-count":0,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T00:00:00Z","timestamp":1782345600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"id":[{"id":"https:\/\/ror.org\/02mhbdp94","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Ministerio de Ciencia Tecnologia e Innovacion de Colombia","award":["1204-937-101846"],"award-info":[{"award-number":["1204-937-101846"]}],"id":[{"id":"https:\/\/ror.org\/03fd5ne08","id-type":"ROR","asserted-by":"crossref"}]},{"name":"University of Antioquia","award":["2024\u009666871"],"award-info":[{"award-number":["2024\u009666871"]}],"id":[{"id":"https:\/\/ror.org\/03bp5hc83","id-type":"ROR","asserted-by":"crossref"}]},{"name":"National Science Foundation","award":["DMR-1829070"],"award-info":[{"award-number":["DMR-1829070"]}]},{"name":"National Institute of General Medical Sciences, National Institutes of Health, and New York State\u0092s Empire State Development Corporation","award":["1-P30-GM124166-01A1"],"award-info":[{"award-number":["1-P30-GM124166-01A1"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"crossref"}]},{"award":["1R01AI172861-01A1"],"award-info":[{"award-number":["1R01AI172861-01A1"]}],"id":[{"id":"https:\/\/ror.org\/043z4tv69","id-type":"ROR","asserted-by":"publisher"}]},{"id":[{"id":"https:\/\/ror.org\/0225cwm17","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,10,6]]},"abstract":"<jats:p>Staphyloxanthin (STX) is a carotenoid synthesized by the human pathogen Staphylococcus aureus, providing this opportunistic pathogen with its characteristic golden color. STX protects Staphylococcus aureus from oxidative stress by scavenging free radical species. Furthermore, STX has been shown to mechanically strengthen the Staphylococcus aureus membrane and to form microdomains that recruit antibiotic-resistance factors, making it an important virulence factor. Thus, inhibition of STX is a promising strategy for intervening against multidrug-resistant strains of this pathogen. The molecular mechanisms by which STX regulates the membrane structure and function of Staphylococcus aureus remain unclear. More specifically, the localization of STX within phosphatidylglycerol (PG) bilayers, the primary phospholipid of this bacterium's membrane, and how this localization drives macroscopic biophysical changes remain unresolved questions. Here, we addressed this issue by integrating molecular dynamics (MD) simulations, X-ray scattering experiments, and fluorescence spectroscopy. We developed an atomistic model of STX, which was validated against X-ray scattering data and which is suitable for all-atom MD simulations. We demonstrate that STX significantly increases lipid packing and acyl chain order of STX-PG bilayer mixtures. In addition, STX self-assembles into clusters, where the long and rigid conjugated triterpenoid chain interdigitates across both leaflets, modifying locally the density of the surrounding PG molecules. These findings provide a molecular explanation to the reduced headgroup spacing and core dynamics observed in fluorescence experiments and are consistent with the formation of structurally-distinct STX-enriched microdomains. Notably, STX reduces the gel-to-liquid crystalline phase transition temperature, indicating a general stabilizing effect for the fluid phase of PG lipids of varying length. Overall, our findings provide molecular insights into how STX enhances the mechanical integrity of PG lipid bilayers and thereby help to establish how membrane remodeling connects with STX's dual roles, acting as an antioxidant and preventing pore formation.<\/jats:p>","DOI":"10.64898\/2026.06.25.732829","type":"posted-content","created":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T05:30:39Z","timestamp":1782451839000},"source":"Crossref","is-referenced-by-count":0,"title":["The Staphylococcus aureus carotenoid staphyloxanthin modifies the structure of phosphatidylglycerol lipid bilayers"],"prefix":"10.64898","author":[{"given":"David Ricardo","family":"Figueroa Blanco","sequence":"first","affiliation":[{"name":"Universidad de los Andes,  Colombia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andres","family":"Ballesteros","sequence":"additional","affiliation":[{"name":"Universidad de los Andes, Colombia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2304-8643","authenticated-orcid":false,"given":"Julian M","family":"Delgado","sequence":"additional","affiliation":[{"name":"National Heart, Lung and Blood Institute, United States of America;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1387-3105","authenticated-orcid":false,"given":"Juan David","family":"Orjuela","sequence":"additional","affiliation":[{"name":"Universidad de los Andes, Colombia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John Erick","family":"Cabrera","sequence":"additional","affiliation":[{"name":"Universidad de los Andes, Colombia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Logan","family":"Hartmann","sequence":"additional","affiliation":[{"name":"Carnegie Mellon University,  United States of America;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jad","family":"Jaber","sequence":"additional","affiliation":[{"name":"University of Pittsburgh,United States of America;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Ji","sequence":"additional","affiliation":[{"name":"Carnegie Mellon University,  United States of America;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucy","family":"Knox","sequence":"additional","affiliation":[{"name":"Carnegie Mellon University,  United States of America;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Suesca","sequence":"additional","affiliation":[{"name":"Universidad de los Andes, Colombia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerson-Dirceu","family":"Lopez","sequence":"additional","affiliation":[{"name":"Universidad de los Andes, Colombia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Carazzone","sequence":"additional","affiliation":[{"name":"Universidad de los Andes, Colombia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2391-7343","authenticated-orcid":false,"given":"Marcela","family":"Manrique-Moreno","sequence":"additional","affiliation":[{"name":"University of Antioquia, Colombia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2262-9179","authenticated-orcid":false,"given":"Gian Pietro","family":"Miscione","sequence":"additional","affiliation":[{"name":"Universidad de los Andes, Colombia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2271-7056","authenticated-orcid":false,"given":"Stephanie","family":"Tristram-Nagle","sequence":"additional","affiliation":[{"name":"Carnegie Mellon University,  United States of America;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6331-8399","authenticated-orcid":false,"given":"Chad","family":"Leidy","sequence":"additional","affiliation":[{"name":"Universidad de los Andes, Colombia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8427-6965","authenticated-orcid":false,"given":"Camilo","family":"Aponte-Santamaria","sequence":"additional","affiliation":[{"name":"Max Planck Institute for Polymer Research, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.06.25.732829","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T14:32:20Z","timestamp":1791297140000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.64898\/2026.06.25.732829"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,25]]},"references-count":0,"URL":"https:\/\/doi.org\/10.64898\/2026.06.25.732829","relation":{},"subject":[],"published":{"date-parts":[[2026,6,25]]},"subtype":"preprint"}}