The Staphylococcus aureus carotenoid staphyloxanthin modifies the structure of phosphatidylglycerol lipid bilayers
- 1Max Planck Institute for Polymer Research, Germany
Abstract
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.
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BibTeX
@misc{blanco2026staphylococcus,
title = {{The Staphylococcus aureus carotenoid staphyloxanthin modifies the structure of phosphatidylglycerol lipid bilayers}},
author = {D. R. Figueroa Blanco and A. Ballesteros and J. M. Delgado and J. D. Orjuela and J. E. Cabrera and L. Hartmann and J. Jaber and K. Ji and L. Knox and E. Suesca and G.-D. Lopez and C. Carazzone and M. Manrique-Moreno and G. P. Miscione and S. Tristram-Nagle and C. Leidy and C. Aponte-Santamaria},
howpublished = {bioRxiv},
year = {2026},
month = jun,
doi = {10.64898/2026.06.25.732829},
url = {https://www.biorxiv.org/content/10.64898/2026.06.25.732829v2},
note = {CC BY},
}
RIS
TY - UNPB
TI - The Staphylococcus aureus carotenoid staphyloxanthin modifies the structure of phosphatidylglycerol lipid bilayers
AU - D. R. Figueroa Blanco
AU - A. Ballesteros
AU - J. M. Delgado
AU - J. D. Orjuela
AU - J. E. Cabrera
AU - L. Hartmann
AU - J. Jaber
AU - K. Ji
AU - L. Knox
AU - E. Suesca
AU - G.-D. Lopez
AU - C. Carazzone
AU - M. Manrique-Moreno
AU - G. P. Miscione
AU - S. Tristram-Nagle
AU - C. Leidy
AU - C. Aponte-Santamaria
PY - 2026
DA - 2026/06/25
PB - bioRxiv
DO - 10.64898/2026.06.25.732829
UR - https://www.biorxiv.org/content/10.64898/2026.06.25.732829v2
AB - 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.
ER -