@article{204426,
  author = {Georgina Benn and Carolina Borrelli and Dheeraj Prakaash and Alex Johnson and Vincent Fideli and Tahj Starr and Dylan Fitzmaurice and Ashton Combs and Martin W{\"u}hr and Enrique Rojas and Syma Khalid and Bart Hoogenboom and Thomas Silhavy},
  title = {OmpA controls order in the outer membrane and shares the mechanical load},
  abstract = {The high resistance of Gram-negative bacteria to antibiotics is largely due to the protein-rich outer membrane (OM) that surrounds these cells. One of the most abundant proteins in the OM is OmpA, with similar proteins found in almost all Gram-negative species. Here, we show the role of OmpA is to order the immobile lattice of other OM proteins and directly couple this lattice with the underlying cell wall (CW). This OmpA-based connection allows the CW and OM protein lattice to behave as a composite material, far stronger than they would be without a direct connection. The high mechanical loads the cell envelope is subjected to are therefore distributed across these layers by OmpA, increasing the survival and virulence of bacteria. OmpA, a predominant outer membrane (OM) protein in Escherichia coli, affects virulence, adhesion, and bacterial OM integrity. However, despite more than 50 y of research, the molecular basis for the role of OmpA has remained elusive. In this study, we demonstrate that OmpA organizes the OM protein lattice and mechanically connects it to the cell wall (CW). Using gene fusions, atomic force microscopy, simulations, and microfluidics, we show that the β-barrel domain of OmpA is critical for maintaining the permeability barrier, but both the β-barrel and CW{\textendash}binding domains are necessary to enhance the cell envelope{\textquoteright}s strength. OmpA integrates the compressive properties of the OM protein lattice with the tensile strength of the CW, forming a mechanically robust composite that increases overall integrity. This coupling likely underpins the ability of the entire envelope to function as a cohesive, resilient structure, critical for the survival of bacteria.},
  year = {2024},
  journal = {Proceedings of the National Academy of Sciences},
  volume = {121},
  number = {50},
  pages = {e2416426121},
  url = {https://www.pnas.org/doi/abs/10.1073/pnas.2416426121},
  doi = {10.1073/pnas.2416426121},
}