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Surveying membrane landscapes: a new look at the bacterial cell surface

Nature Reviews Microbiology volume 21, pages 502–518 (2023)Cite this article

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Abstract

Recent studies applying advanced imaging techniques are changing the way we understand bacterial cell surfaces, bringing new knowledge on everything from single-cell heterogeneity in bacterial populations to their drug sensitivity and mechanisms of antimicrobial resistance. In both Gram-positive and Gram-negative bacteria, the outermost surface of the bacterial cell is being imaged at nanoscale; as a result, topographical maps of bacterial cell surfaces can be constructed, revealing distinct zones and specific features that might uniquely identify each cell in a population. Functionally defined assembly precincts for protein insertion into the membrane have been mapped at nanoscale, and equivalent lipid-assembly precincts are suggested from discrete lipopolysaccharide patches. As we review here, particularly for Gram-negative bacteria, the applications of various modalities of nanoscale imaging are reawakening our curiosity about what is conceptually a 3D cell surface landscape: what it looks like, how it is made and how it provides resilience to respond to environmental impacts.

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Fig. 1: Surface features of Gram-positive and Gram-negative bacteria.
Fig. 2: Mapping the surface of an Escherichia coli cell.
Fig. 3: Establishing the cell surface in Gram-negative bacteria.
Fig. 4: Bracing and breaching the cell surface of Gram-negative bacteria.

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References

  1. Nikaido, H. in Escherichia coli and Salmonella Cellular and Molecular Biology Vol. 1 (eds Neidhardt, F. C. et al.) Ch. 5, 29–47 (ASM Press, 1996).

  2. Greening, C. & Lithgow, T. Formation and function of bacterial organelles. Nat. Rev. Microbiol. 18, 677–689 (2020).

    Article  CAS  PubMed  Google Scholar 

  3. Cambré, A. & Aertsen, A. Bacterial vivisection: how fluorescence-based imaging techniques shed a light on the inner workings of bacteria. Microbiol Mol. Biol. Rev. https://doi.org/10.1128/MMBR.00008-20 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  4. Flechsler, J., Heimerl, T., Huber, H., Rachel, R. & Berg, I. A. Functional compartmentalization and metabolic separation in a prokaryotic cell. Proc. Natl Acad. Sci. USA https://doi.org/10.1073/pnas.2022114118 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  5. Tocheva, E. I., Ortega, D. R. & Jensen, G. J. Sporulation, bacterial cell envelopes and the origin of life. Nat. Rev. Microbiol. 14, 535–542 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  6. Rohde, M. The Gram-positive bacterial cell wall. Microbiol. Spectr. https://doi.org/10.1128/microbiolspec.GPP3-0044-2018 (2019).

    Article  PubMed  Google Scholar 

  7. Pasquina-Lemonche, L. et al. The architecture of the Gram-positive bacterial cell wall. Nature 582, 294–297 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Chen, Y. Y. et al. Surface rigidity change of Escherichia coli after filamentous bacteriophage infection. Langmuir 25, 4607–4614 (2009).

    Article  CAS  PubMed  Google Scholar 

  9. Benn, G. et al. Phase separation in the outer membrane of Escherichia coli. Proc. Natl Acad. Sci. USA https://doi.org/10.1073/pnas.2112237118 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  10. Oestreicher, Z., Taoka, A. & Fukumori, Y. A comparison of the surface nanostructure from two different types of Gram-negative cells: Escherichia coli and Rhodobacter sphaeroides. Micron 72, 8–14 (2015).

    Article  PubMed  Google Scholar 

  11. Stokes, J. M. et al. Pentamidine sensitizes Gram-negative pathogens to antibiotics and overcomes acquired colistin resistance. Nat. Microbiol. 2, 17028 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  12. French, S. et al. Potentiation of antibiotics against Gram-negative bacteria by polymyxin B analogue SPR741 from unique perturbation of the outer membrane. ACS Infect. Dis. 6, 1405–1412 (2020).

    Article  CAS  PubMed  Google Scholar 

  13. Kotra, L. P., Golemi, D., Amro, N. A., Liu, G.-Y. & Mobashery, S. Dynamics of the lipopolysaccharide assembly on the surface of Escherichia coli. J. Am. Chem. Soc. 121, 8707–8711 (1999).

    Article  CAS  Google Scholar 

  14. Amro, N. A. et al. High-resolution atomic force microscopy studies of the Escherichia coli outer membrane: structural basis for permeability. Langmuir 16, 2789–2796 (2000).

    Article  CAS  Google Scholar 

  15. Benn, G., Pyne, A. L. B., Ryadnov, M. G. & Hoogenboom, B. W. Imaging live bacteria at the nanoscale: comparison of immobilisation strategies. Analyst 144, 6944–6952 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Wisniewski, J. R. & Rakus, D. Multi-enzyme digestion FASP and the ‘Total Protein Approach’-based absolute quantification of the Escherichia coli proteome. J. Proteom. 109, 322–331 (2014).

    Article  CAS  Google Scholar 

  17. Neidhardt, F. C. & Umbarger, H. E. in Escherichia coli and Salmonella Cellular and Molecular Biology Vol. 1 (eds Neidhardt, F. C. et al.) Ch. 3, 13–16 (ASM Press, 1996).

  18. Koebnik, R., Locher, K. P. & Van Gelder, P. Structure and function of bacterial outer membrane proteins: barrels in a nutshell. Mol. Microbiol. 37, 239–253 (2000).

    Article  CAS  PubMed  Google Scholar 

  19. Fairman, J. W., Noinaj, N. & Buchanan, S. K. The structural biology of β-barrel membrane proteins: a summary of recent reports. Curr. Opin. Struct. Biol. 21, 523–531 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Prajapati, J. D., Kleinekathöfer, U. & Winterhalter, M. How to enter a bacterium: bacterial porins and the permeation of antibiotics. Chem. Rev. 121, 5158–5192 (2021).

    Article  CAS  PubMed  Google Scholar 

  21. Marzoa, J. et al. Analysis of outer membrane porin complexes of Neisseria meningitidis in wild-type and specific knock-out mutant strains. Proteomics 9, 648–656 (2009).

    Article  CAS  PubMed  Google Scholar 

  22. Deo, P. et al. Outer membrane vesicles from Neisseria gonorrhoeae target PorB to mitochondria and induce apoptosis. PLoS Pathog. 14, e1006945 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  23. Pratt, L. A., Hsing, W., Gibson, K. E. & Silhavy, T. J. From acids to osmZ: multiple factors influence synthesis of the OmpF and OmpC porins in Escherichia coli. Mol. Microbiol. 20, 911–917 (1996).

    Article  CAS  PubMed  Google Scholar 

  24. Martínez, J. L. & Rojo, F. Metabolic regulation of antibiotic resistance. FEMS Microbiol. Rev. 35, 768–789 (2011).

    Article  PubMed  Google Scholar 

  25. De la Cruz, M. Á. & Calva, E. The complexities of porin genetic regulation. J. Mol. Microbiol. Biotechnol. 18, 24–36 (2010).

    PubMed  Google Scholar 

  26. Doménech-Sánchez, A., Hernández-Allés, S., Martínez-Martínez, L., Benedí, V. J. & Albertí, S. Identification and characterization of a new porin gene of Klebsiella pneumoniae: its role in β-lactam antibiotic resistance. J. Bacteriol. 181, 2726–2732 (1999).

    Article  PubMed  PubMed Central  Google Scholar 

  27. Sugawara, E., Kojima, S. & Nikaido, H. Klebsiella pneumoniae major porins OmpK35 and OmpK36 allow more efficient diffusion of β-lactams than their Escherichia coli homologs OmpF and OmpC. J. Bacteriol. 198, 3200–3208 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Rocker, A. et al. Global trends in proteome remodeling of the outer membrane modulate antimicrobial permeability in Klebsiella pneumoniae. mBio https://doi.org/10.1128/mBio.00603-20 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  29. Macklin, D. N., Ruggero, N. A. & Covert, M. W. The future of whole-cell modeling. Curr. Opin. Biotechnol. 28, 111–115 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Toni, T., Jovanovic, G., Huvet, M., Buck, M. & Stumpf, M. P. From qualitative data to quantitative models: analysis of the phage shock protein stress response in Escherichia coli. BMC Syst. Biol. 5, 69 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  31. Liu, F., Assaf, G., Chen, M. & Heiner, M. A Petri nets-based framework for whole-cell modeling. Biosystems 210, 104533 (2021).

    Article  PubMed  Google Scholar 

  32. Kirk, P. D., Babtie, A. C. & Stumpf, M. P. Systems biology (un)certainties. Science 350, 386–388 (2015).

    Article  CAS  PubMed  Google Scholar 

  33. Rassam, P. et al. Supramolecular assemblies underpin turnover of outer membrane proteins in bacteria. Nature 523, 333–336 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Brown, A. I. & Sivak, D. A. Theory of nonequilibrium free energy transduction by molecular machines. Chem. Rev. 120, 434–459 (2020).

    Article  CAS  PubMed  Google Scholar 

  35. Chavent, M. et al. How nanoscale protein interactions determine the mesoscale dynamic organisation of bacterial outer membrane proteins. Nat. Commun. 9, 2846 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  36. Hell, S. W. Microscopy and its focal switch. Nat. Methods 6, 24–32 (2009).

    Article  CAS  PubMed  Google Scholar 

  37. Huang, B., Babcock, H. & Zhuang, X. Breaking the diffraction barrier: super-resolution imaging of cells. Cell 143, 1047–1058 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Lippincott-Schwartz, J. & Patterson, G. H. Photoactivatable fluorescent proteins for diffraction-limited and super-resolution imaging. Trends Cell Biol. 19, 555–565 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Kamiyama, D. & Huang, B. Development in the STORM. Dev. Cell 23, 1103–1110 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Rust, M. J., Bates, M. & Zhuang, X. Sub-diffraction-limit imaging by stochastic optical reconstruction microscopy (STORM). Nat. Methods 3, 793–795 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Gunasinghe, S. D., Webb, C. T., Elgass, K. D., Hay, I. D. & Lithgow, T. Super-resolution imaging of protein secretion systems and the cell surface of Gram-negative bacteria. Front. Cell Infect. Microbiol. 7, 220 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  42. Gunasinghe, S. D. et al. The WD40 protein BamB mediates coupling of BAM complexes into assembly precincts in the bacterial outer membrane. Cell Rep. 23, 2782–2794 (2018).

    Article  CAS  PubMed  Google Scholar 

  43. Webb, C. T. et al. Dynamic association of BAM complex modules includes surface exposure of the lipoprotein BamC. J. Mol. Biol. 422, 545–555 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Noinaj, N., Gumbart, J. C. & Buchanan, S. K. The β-barrel assembly machinery in motion. Nat. Rev. Microbiol. 15, 197–204 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Doyle, M. T. & Bernstein, H. D. BamA forms a translocation channel for polypeptide export across the bacterial outer membrane. Mol. Cell 81, 2000–2012.e3 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Doyle, M. T. et al. Cryo-EM structures reveal multiple stages of bacterial outer membrane protein folding. Cell 185, 1143–1156.e13 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Horne, J. E. & Radford, S. E. Roll out the barrel! Outer membrane tension resolves an unexpected folding intermediate. Cell 185, 1107–1109 (2022).

    Article  CAS  PubMed  Google Scholar 

  48. Dong, H., Sarkes, D. A., Stratis-Cullum, D. N. & Hurley, M. M. Direct conjugation of fluorescent quantum dots with E. coli via surface-displayed histidine-containing peptides. Colloids Surf. B Biointerfaces 203, 111730 (2021).

    Article  CAS  PubMed  Google Scholar 

  49. Yang, C., Xie, H., Li, Q.-C., Sun, E.-J. & Su, B.-L. Adherence and interaction of cationic quantum dots on bacterial surfaces. J. Colloid Interface Sci. 450, 388–395 (2015).

    Article  CAS  PubMed  Google Scholar 

  50. Dong, H. et al. Living bacteria-nanoparticle hybrids mediated through surface-displayed peptides. Langmuir 34, 5837–5848 (2018).

    Article  CAS  PubMed  Google Scholar 

  51. Smit, J. & Nikaido, H. Outer membrane of Gram-negative bacteria. XVIII. Electron microscopic studies on porin insertion sites and growth of cell surface of Salmonella typhimurium. J. Bacteriol. 135, 687–702 (1978).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Reid, J., Fung, H., Gehring, K., Klebba, P. E. & Nikaido, H. Targeting of porin to the outer membrane of Escherichia coli. Rate of trimer assembly and identification of a dimer intermediate. J. Biol. Chem. 263, 7753–7759 (1988).

    Article  CAS  PubMed  Google Scholar 

  53. Jansen, C., Heutink, M., Tommassen, J. & de Cock, H. The assembly pathway of outer membrane protein PhoE of Escherichia coli. Eur. J. Biochem. 267, 3792–3800 (2000).

    Article  CAS  PubMed  Google Scholar 

  54. Stubenrauch, C. et al. Effective assembly of fimbriae in Escherichia coli depends on the translocation assembly module nanomachine. Nat. Microbiol. 1, 16064 (2016).

    Article  CAS  PubMed  Google Scholar 

  55. Jarosławski, S., Duquesne, K., Sturgis, J. N. & Scheuring, S. High-resolution architecture of the outer membrane of the Gram-negative bacteria Roseobacter denitrificans. Mol. Microbiol. 74, 1211–1222 (2009).

    Article  PubMed  Google Scholar 

  56. Sundararaj, S. et al. The CyberCell Database (CCDB): a comprehensive, self-updating, relational database to coordinate and facilitate in silico modeling of Escherichia coli. Nucleic Acids Res. 32, D293–D295 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Webby, M. N. et al. Lipids mediate supramolecular outer membrane protein assembly in bacteria. Sci. Adv. 8, eadc9566 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Danoff, E. J. & Fleming, K. G. Membrane defects accelerate outer membrane β-barrel protein folding. Biochemistry 54, 97–99 (2015).

    Article  CAS  PubMed  Google Scholar 

  59. Horne, J. E., Brockwell, D. J. & Radford, S. E. Role of the lipid bilayer in outer membrane protein folding in Gram-negative bacteria. J. Biol. Chem. 295, 10340–10367 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Ghosh, A. S. & Young, K. D. Helical disposition of proteins and lipopolysaccharide in the outer membrane of Escherichia coli. J. Bacteriol. 187, 1913–1922 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Shrivastava, R. & Chng, S. S. Lipid trafficking across the Gram-negative cell envelope. J. Biol. Chem. 294, 14175–14184 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Lundstedt, E., Kahne, D. & Ruiz, N. Assembly and maintenance of lipids at the bacterial outer membrane. Chem. Rev. 121, 5098–5123 (2021).

    Article  CAS  PubMed  Google Scholar 

  63. Bishop, R. E. Ratcheting up lipopolysaccharide transport. Nature 567, 471–472 (2019).

    Article  CAS  PubMed  Google Scholar 

  64. Guest, R. L., Rutherford, S. T. & Silhavy, T. J. Border control: regulating LPS biogenesis. Trends Microbiol. 29, 334–345 (2021).

    Article  CAS  PubMed  Google Scholar 

  65. Gibbs, K. A. et al. Complex spatial distribution and dynamics of an abundant Escherichia coli outer membrane protein, LamB. Mol. Microbiol. 53, 1771–1783 (2004).

    Article  CAS  PubMed  Google Scholar 

  66. Spector, J. et al. Mobility of BtuB and OmpF in the Escherichia coli outer membrane: implications for dynamic formation of a translocon complex. Biophys. J. 99, 3880–3886 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Rothenberg, E. et al. Single-virus tracking reveals a spatial receptor-dependent search mechanism. Biophys. J. 100, 2875–2882 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Ursell, T. S., Trepagnier, E. H., Huang, K. C. & Theriot, J. A. Analysis of surface protein expression reveals the growth pattern of the Gram-negative outer membrane. PLoS Comput. Biol. 8, e1002680 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Mamou, G. et al. Peptidoglycan maturation controls outer membrane protein assembly. Nature 606, 953–959 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Wang, H., Wingreen, N. S. & Mukhopadhyay, R. Self-organized periodicity of protein clusters in growing bacteria. Phys. Rev. Lett. 101, 218101 (2008).

    Article  PubMed  Google Scholar 

  71. Vos-Scheperkeuter, G. H., Pas, E., Brakenhoff, G. J., Nanninga, N. & Witholt, B. Topography of the insertion of LamB protein into the outer membrane of Escherichia coli wild-type and lac-lamB cells. J. Bacteriol. 159, 440–447 (1984).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Noinaj, N., Guillier, M., Barnard, T. J. & Buchanan, S. K. TonB-dependent transporters: regulation, structure, and function. Annu. Rev. Microbiol. 64, 43–60 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Nierman, W. C. et al. Complete genome sequence of Caulobacter crescentus. Proc. Natl Acad. Sci. USA 98, 4136–4141 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Anwari, K. et al. A modular BAM complex in the outer membrane of the α-proteobacterium Caulobacter crescentus. PLoS ONE 5, e8619 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  75. Ferguson, A. D., Hofmann, E., Coulton, J. W., Diederichs, K. & Welte, W. Siderophore-mediated iron transport: crystal structure of FhuA with bound lipopolysaccharide. Science 282, 2215–2220 (1998).

    Article  CAS  PubMed  Google Scholar 

  76. Locher, K. P. et al. Transmembrane signaling across the ligand-gated FhuA receptor: crystal structures of free and ferrichrome-bound states reveal allosteric changes. Cell 95, 771–778 (1998).

    Article  CAS  PubMed  Google Scholar 

  77. Pawelek, P. D. et al. Structure of TonB in complex with FhuA, E. coli outer membrane receptor. Science 312, 1399–1402 (2006).

    Article  CAS  PubMed  Google Scholar 

  78. Buchanan, S. K. et al. Crystal structure of the outer membrane active transporter FepA from Escherichia coli. Nat. Struct. Biol. 6, 56–63 (1999).

    Article  CAS  PubMed  Google Scholar 

  79. Grinter, R. & Lithgow, T. The structure of the bacterial iron-catecholate transporter Fiu suggests that it imports substrates via a two-step mechanism. J. Biol. Chem. 294, 19523–19534 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Grinter, R. & Lithgow, T. Determination of the molecular basis for coprogen import by Gram-negative bacteria. IUCrJ 6, 401–411 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Grinter, R. & Lithgow, T. The crystal structure of the TonB-dependent transporter YncD reveals a positively charged substrate-binding site. Acta Crystallogr. D. Struct. Biol. 76, 484–495 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Ratliff, A. C., Buchanan, S. K. & Celia, H. The Ton motor. Front. Microbiol. 13, 852955 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  83. Larsen, R. A., Thomas, M. G. & Postle, K. Protonmotive force, ExbB and ligand-bound FepA drive conformational changes in TonB. Mol. Microbiol. 31, 1809–1824 (1999).

    Article  CAS  PubMed  Google Scholar 

  84. Kaserer, W. A. et al. Insight from TonB hybrid proteins into the mechanism of iron transport through the outer membrane. J. Bacteriol. 190, 4001–4016 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Freed, D. M., Lukasik, S. M., Sikora, A., Mokdad, A. & Cafiso, D. S. Monomeric TonB and the Ton box are required for the formation of a high-affinity transporter-TonB complex. Biochemistry 52, 2638–2648 (2013).

    Article  CAS  PubMed  Google Scholar 

  86. Gresock, M. G., Kastead, K. A. & Postle, K. From homodimer to heterodimer and back: elucidating the TonB energy transduction cycle. J. Bacteriol. 197, 3433–3445 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Sarver, J. L., Zhang, M., Liu, L., Nyenhuis, D. & Cafiso, D. S. A dynamic protein–protein coupling between the TonB-dependent transporter FhuA and TonB. Biochemistry 57, 1045–1053 (2018).

    Article  CAS  PubMed  Google Scholar 

  88. Josts, I., Veith, K. & Tidow, H. Ternary structure of the outer membrane transporter FoxA with resolved signalling domain provides insights into TonB-mediated siderophore uptake. eLife https://doi.org/10.7554/eLife.48528 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  89. Irastortza-Olaziregi, M. & Amster-Choder, O. RNA localization in prokaryotes: where, when, how, and why. Wiley Interdiscip. Rev. RNA 12, e1615 (2021).

    Article  CAS  PubMed  Google Scholar 

  90. Kannaiah, S., Livny, J. & Amster-Choder, O. Spatiotemporal organization of the E. coli transcriptome: translation independence and engagement in regulation. Mol. Cell 76, 574–589.e7 (2019).

    Article  CAS  PubMed  Google Scholar 

  91. Moffitt, J. R., Pandey, S., Boettiger, A. N., Wang, S. & Zhuang, X. Spatial organization shapes the turnover of a bacterial transcriptome. eLife https://doi.org/10.7554/eLife.13065 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  92. Brandon, L. D. et al. IcsA, a polarly localized autotransporter with an atypical signal peptide, uses the Sec apparatus for secretion, although the Sec apparatus is circumferentially distributed. Mol. Microbiol. 50, 45–60 (2003).

    Article  CAS  PubMed  Google Scholar 

  93. Espeli, O., Nurse, P., Levine, C., Lee, C. & Marians, K. J. SetB: an integral membrane protein that affects chromosome segregation in Escherichia coli. Mol. Microbiol. 50, 495–509 (2003).

    Article  CAS  PubMed  Google Scholar 

  94. Lycklama, A. N. J. A. & Driessen, A. J. The bacterial Sec-translocase: structure and mechanism. Philos. Trans. R. Soc. Lond. B Biol. Sci. 367, 1016–1028 (2012).

    Article  Google Scholar 

  95. Komar, J. et al. Membrane protein insertion and assembly by the bacterial holo-translocon SecYEG-SecDF-YajC-YidC. Biochem. J. 473, 3341–3354 (2016).

    Article  CAS  PubMed  Google Scholar 

  96. Wang, Y. et al. A supercomplex spanning the inner and outer membranes mediates the biogenesis of β-barrel outer membrane proteins in bacteria. J. Biol. Chem. 291, 16720–16729 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Carlson, M. L. et al. Profiling the Escherichia coli membrane protein interactome captured in Peptidisc libraries. eLife https://doi.org/10.7554/eLife.46615 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  98. Alvira, S. et al. Inter-membrane association of the Sec and BAM translocons for bacterial outer-membrane biogenesis. eLife https://doi.org/10.7554/eLife.60669 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  99. Troman, L. & Collinson, I. Pushing the envelope: the mysterious journey through the bacterial secretory machinery, and beyond. Front. Microbiol. 12, 782900 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  100. Tsukazaki, T. Structure-based working model of SecDF, a proton-driven bacterial protein translocation factor. FEMS Microbiol. Lett. https://doi.org/10.1093/femsle/fny112 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  101. Lyu, Z. X. & Zhao, X. S. Periplasmic quality control in biogenesis of outer membrane proteins. Biochem. Soc. Trans. 43, 133–138 (2015).

    Article  CAS  PubMed  Google Scholar 

  102. Mas, G., Thoma, J. & Hiller, S. The periplasmic chaperones Skp and SurA. Subcell. Biochem. 92, 169–186 (2019).

    Article  CAS  PubMed  Google Scholar 

  103. Schiffrin, B. et al. Dynamic interplay between the periplasmic chaperone SurA and the BAM complex in outer membrane protein folding. Commun. Biol. 5, 560 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Collin, S., Guilvout, I., Chami, M. & Pugsley, A. P. YaeT-independent multimerization and outer membrane association of secretin PulD. Mol. Microbiol. 64, 1350–1357 (2007).

    Article  CAS  PubMed  Google Scholar 

  105. Dunstan, R. A. et al. Assembly of the secretion pores GspD, Wza and CsgG into bacterial outer membranes does not require the Omp85 proteins BamA or TamA. Mol. Microbiol. 97, 616–629 (2015).

    Article  CAS  PubMed  Google Scholar 

  106. Daefler, S. & Russel, M. The Salmonella typhimurium InvH protein is an outer membrane lipoprotein required for the proper localization of InvG. Mol. Microbiol. 28, 1367–1380 (1998).

    Article  CAS  PubMed  Google Scholar 

  107. Burghout, P. et al. Role of the pilot protein YscW in the biogenesis of the YscC secretin in Yersinia enterocolitica. J. Bacteriol. 186, 5366–5375 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Cao, B. et al. Structure of the nonameric bacterial amyloid secretion channel. Proc. Natl Acad. Sci. USA 111, E5439–E5444 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Goyal, P. et al. Structural and mechanistic insights into the bacterial amyloid secretion channel CsgG. Nature 516, 250–253 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Matsumoto, K., Hara, H., Fishov, I., Mileykovskaya, E. & Norris, V. The membrane: transertion as an organizing principle in membrane heterogeneity. Front. Microbiol. 6, 572 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  111. Hay, I. D., Belousoff, M. J., Dunstan, R. A., Bamert, R. S. & Lithgow, T. Structure and membrane topography of the Vibrio-type secretin complex from the type 2 secretion system of enteropathogenic Escherichia coli. J. Bacteriol. https://doi.org/10.1128/JB.00521-17 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  112. Douzi, B. et al. Unraveling the self-assembly of the Pseudomonas aeruginosa XcpQ secretin periplasmic domain provides new molecular insights into type II secretion system secreton architecture and dynamics. mBio https://doi.org/10.1128/mBio.01185-17 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  113. Yan, Z., Yin, M., Xu, D., Zhu, Y. & Li, X. Structural insights into the secretin translocation channel in the type II secretion system. Nat. Struct. Mol. Biol. 24, 177–183 (2017).

    Article  CAS  PubMed  Google Scholar 

  114. Worrall, L. J. et al. Near-atomic-resolution cryo-EM analysis of the Salmonella T3S injectisome basal body. Nature 540, 597–601 (2016).

    Article  CAS  PubMed  Google Scholar 

  115. Conners, R. et al. CryoEM structure of the outer membrane secretin channel pIV from the f1 filamentous bacteriophage. Nat. Commun. 12, 6316 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Dal Peraro, M. & van der Goot, F. G. Pore-forming toxins: ancient, but never really out of fashion. Nat. Rev. Microbiol. 14, 77–92 (2016).

    Article  PubMed  Google Scholar 

  117. Bayly-Jones, C., Bubeck, D. & Dunstone, M. A. The mystery behind membrane insertion: a review of the complement membrane attack complex. Philos. Trans. R. Soc. Lond. B Biol. Sci. https://doi.org/10.1098/rstb.2016.0221 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  118. van der Mei, H. C. & Busscher, H. J. Bacterial cell surface heterogeneity: a pathogen’s disguise. PLoS Pathog. 8, e1002821 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  119. Davis, K. M. & Isberg, R. R. Defining heterogeneity within bacterial populations via single cell approaches. Bioessays 38, 782–790 (2016).

    Article  PubMed  Google Scholar 

  120. Rojas, E. R. et al. The outer membrane is an essential load-bearing element in Gram-negative bacteria. Nature 559, 617–621 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Mathelié-Guinlet, M., Asmar, A. T., Collet, J. F. & Dufrêne, Y. F. Bacterial cell mechanics beyond peptidoglycan. Trends Microbiol. 28, 706–708 (2020).

    Article  PubMed  Google Scholar 

  122. Sun, J., Rutherford, S. T., Silhavy, T. J. & Huang, K. C. Physical properties of the bacterial outer membrane. Nat. Rev. Microbiol. 20, 236–248 (2022).

    Article  CAS  PubMed  Google Scholar 

  123. Avraham, R. et al. Pathogen cell-to-cell variability drives heterogeneity in host immune responses. Cell 162, 1309–1321 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Reyes Ruiz, L. M., Williams, C. L. & Tamayo, R. Enhancing bacterial survival through phenotypic heterogeneity. PLoS Pathog. 16, e1008439 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Sun, Y.-J. et al. Probing bacterial cell wall growth by tracing wall-anchored protein complexes. Nat. Commun. 12, 2160 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Salinas-Almaguer, S. et al. Membrane rigidity regulates E. coli proliferation rates. Sci. Rep. 12, 933 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Joly, N. et al. Managing membrane stress: the phage shock protein (Psp) response, from molecular mechanisms to physiology. FEMS Microbiol. Rev. 34, 797–827 (2010).

    Article  CAS  PubMed  Google Scholar 

  128. Hwang, H., Paracini, N., Parks, J. M., Lakey, J. H. & Gumbart, J. C. Distribution of mechanical stress in the Escherichia coli cell envelope. Biochim. Biophys. Acta Biomembr. 1860, 2566–2575 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Egan, A. J. F., Errington, J. & Vollmer, W. Regulation of peptidoglycan synthesis and remodelling. Nat. Rev. Microbiol. 18, 446–460 (2020).

    Article  CAS  PubMed  Google Scholar 

  130. Pavlova, A., Hwang, H., Lundquist, K., Balusek, C. & Gumbart, J. C. Living on the edge: simulations of bacterial outer-membrane proteins. Biochim. Biophys. Acta 1858, 1753–1759 (2016).

    Article  CAS  PubMed  Google Scholar 

  131. Vaiwala, R., Sharma, P., Puranik, M. & Ayappa, K. G. Developing a coarse-grained model for bacterial cell walls: evaluating mechanical properties and free energy barriers. J. Chem. Theory Comput. 16, 5369–5384 (2020).

    Article  CAS  PubMed  Google Scholar 

  132. Yap, L.-W. & Endres, R. G. A model of cell-wall dynamics during sporulation in Bacillus subtilis. Soft Matter 13, 8089–8095 (2017).

    Article  CAS  PubMed  Google Scholar 

  133. Stumpf, M. P., Robertson, B. D., Duncan, K. & Young, D. B. Systems biology and its impact on anti-infective drug development. Prog. Drug Res. 64, 3–20 (2007).

    Google Scholar 

  134. Xavier, J. B. et al. Mathematical models to study the biology of pathogens and the infectious diseases they cause. iScience 25, 104079 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Asmar, A. T. et al. Communication across the bacterial cell envelope depends on the size of the periplasm. PLoS Biol. 15, e2004303 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  136. Cohen, E. J., Ferreira, J. L., Ladinsky, M. S., Beeby, M. & Hughes, K. T. Nanoscale-length control of the flagellar driveshaft requires hitting the tethered outer membrane. Science 356, 197–200 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  137. Mandela, E. et al. Adaptation of the periplasm to maintain spatial constraints essential for cell envelope processes and cell viability. eLife https://doi.org/10.7554/eLife.73516 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  138. Santos, T. C., Silva, M. A., Morgado, L., Dantas, J. M. & Salgueiro, C. A. Diving into the redox properties of Geobacter sulfurreducens cytochromes: a model for extracellular electron transfer. Dalton Trans. 44, 9335–9344 (2015).

    Article  CAS  PubMed  Google Scholar 

  139. Jiménez Otero, F., Chan, C. H. & Bond, D. R. Identification of different putative outer membrane electron conduits necessary for Fe(III) citrate, Fe(III) oxide, Mn(IV) oxide, or electrode reduction by Geobacter sulfurreducens. J. Bacteriol. https://doi.org/10.1128/JB.00347-18 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  140. Reguera, G. & Kashefi, K. The electrifying physiology of Geobacter bacteria, 30 years on. Adv. Microb. Physiol. 74, 1–96 (2019).

    Article  PubMed  Google Scholar 

  141. Wang, F. et al. Structure of Geobacter OmcZ filaments suggests extracellular cytochrome polymers evolved independently multiple times. eLife 11, e81551 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  142. Selkrig, J. et al. Discovery of an archetypal protein transport system in bacterial outer membranes. Nat. Struct. Mol. Biol. 19, 506–510 (2012).

    Article  CAS  PubMed  Google Scholar 

  143. Shen, H.-H. et al. Reconstitution of a nanomachine driving the assembly of proteins into bacterial outer membranes. Nat. Commun. 5, 5078 (2014).

    Article  CAS  PubMed  Google Scholar 

  144. Selkrig, J. et al. Conserved features in TamA enable interaction with TamB to drive the activity of the translocation and assembly module. Sci. Rep. 5, 12905 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  145. Heinz, E., Selkrig, J., Belousoff, M. J. & Lithgow, T. Evolution of the translocation and assembly module (TAM). Genome Biol. Evol. 7, 1628–1643 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  146. Stubenrauch, C. J., Bamert, R. S., Wang, J. & Lithgow, T. A noncanonical chaperone interacts with drug efflux pumps during their assembly into bacterial outer membranes. PLoS Biol. 20, e3001523 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  147. Heinz, E. & Lithgow, T. A comprehensive analysis of the Omp85/TpsB protein superfamily structural diversity, taxonomic occurrence, and evolution. Front. Microbiol. 5, 370 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  148. Iqbal, H., Kenedy, M. R., Lybecker, M. & Akins, D. R. The TamB ortholog of Borrelia burgdorferi interacts with the β-barrel assembly machine (BAM) complex protein BamA. Mol. Microbiol. 102, 757–774 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  149. Jung, H. J., Sorbara, M. T. & Pamer, E. G. TAM mediates adaptation of carbapenem-resistant Klebsiella pneumoniae to antimicrobial stress during host colonization and infection. PLoS Pathog. 17, e1009309 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  150. Bialer, M. G. et al. MapB, the Brucella suis TamB homologue, is involved in cell envelope biogenesis, cell division and virulence. Sci. Rep. 9, 2158 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  151. Kessel, M., Radermacher, M. & Frank, J. The structure of the stalk surface layer of a brine pond microorganism: correlation averaging applied to a double layered lattice structure. J. Microsc. 139, 63–74 (1985).

    Article  CAS  PubMed  Google Scholar 

  152. Chalcroft, J. P., Engelhardt, H. & Baumeister, W. Structure of the porin from a bacterial stalk. FEBS Lett. 211, 53–58 (1987).

    Article  CAS  PubMed  Google Scholar 

  153. Yamashita, H. et al. Single-molecule imaging on living bacterial cell surface by high-speed AFM. J. Mol. Biol. 422, 300–309 (2012).

    Article  CAS  PubMed  Google Scholar 

  154. Kessel, M., Brennan, M. J., Trus, B. L., Bisher, M. E. & Steven, A. C. Naturally crystalline porin in the outer membrane of Bordetella pertussis. J. Mol. Biol. 203, 275–278 (1988).

    Article  CAS  PubMed  Google Scholar 

  155. Amako, K., Wai, S. N., Umeda, A., Shigematsu, M. & Takade, A. Electron microscopy of the major outer membrane protein of Campylobacter jejuni. Microbiol. Immunol. 40, 749–754 (1996).

    Article  CAS  PubMed  Google Scholar 

  156. Gonçalves, R. P., Buzhynskyy, N., Prima, V., Sturgis, J. N. & Scheuring, S. Supramolecular assembly of VDAC in native mitochondrial outer membranes. J. Mol. Biol. 369, 413–418 (2007).

    Article  PubMed  Google Scholar 

  157. Typas, A., Banzhaf, M., Gross, C. A. & Vollmer, W. From the regulation of peptidoglycan synthesis to bacterial growth and morphology. Nat. Rev. Microbiol. 10, 123–136 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  158. Brown, P. J., Kysela, D. T. & Brun, Y. V. Polarity and the diversity of growth mechanisms in bacteria. Semin. Cell Dev. Biol. 22, 790–798 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  159. Brown, P. J. et al. Polar growth in the alphaproteobacterial order Rhizobiales. Proc. Natl Acad. Sci. USA 109, 1697–1701 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  160. Vassen, V. et al. Localized incorporation of outer membrane components in the pathogen Brucella abortus. EMBO J. https://doi.org/10.15252/embj.2018100323 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  161. Jeong, H. et al. Genome sequences of Escherichia coli B strains REL606 and BL21(DE3). J. Mol. Biol. 394, 644–652 (2009).

    Article  CAS  PubMed  Google Scholar 

  162. Chart, H., Smith, H. R., La Ragione, R. M. & Woodward, M. J. An investigation into the pathogenic properties of Escherichia coli strains BLR, BL21, DH5α and EQ1. J. Appl. Microbiol. 89, 1048–1058 (2000).

    Article  CAS  PubMed  Google Scholar 

  163. Liu, D. & Reeves, P. R. Escherichia coli K12 regains its O antigen. Microbiology 140, 49–57 (1994).

    Article  CAS  PubMed  Google Scholar 

  164. Antimicrobial Resistance, C. Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis. Lancet 399, 629–655 (2022).

    Article  Google Scholar 

  165. Ho, P. L. et al. Characterization of carbapenem-resistant Escherichia coli and Klebsiella pneumoniae from a healthcare region in Hong Kong. Eur. J. Clin. Microbiol. Infect. Dis. 35, 379–385 (2016).

    Article  CAS  PubMed  Google Scholar 

  166. Hao, M. et al. Porin deficiency in carbapenem-resistant Enterobacter aerogenes strains. Microb. Drug Resist. 24, 1277–1283 (2018).

    Article  CAS  PubMed  Google Scholar 

  167. Tian, X. et al. First description of antimicrobial resistance in carbapenem-susceptible Klebsiella pneumoniae after imipenem treatment, driven by outer membrane remodeling. BMC Microbiol. 20, 218 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  168. Li, Y. et al. Identification of a compound that inhibits the growth of Gram-negative bacteria by blocking BamA–BamD interaction. Front. Microbiol. 11, 1252 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  169. Srinivas, N. et al. Peptidomimetic antibiotics target outer-membrane biogenesis in Pseudomonas aeruginosa. Science 327, 1010–1013 (2010).

    Article  CAS  PubMed  Google Scholar 

  170. Hagan, C. L., Wzorek, J. S. & Kahne, D. Inhibition of the β-barrel assembly machine by a peptide that binds BamD. Proc. Natl Acad. Sci. USA 112, 2011–2016 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  171. Sousa, M. C. New antibiotics target the outer membrane of bacteria. Nature 576, 389–390 (2019).

    Article  CAS  PubMed  Google Scholar 

  172. Steenhuis, M., van Ulsen, P., Martin, N. I. & Luirink, J. A ban on BAM: an update on inhibitors of the β-barrel assembly machinery. FEMS Microbiol. Lett. https://doi.org/10.1093/femsle/fnab059 (2021).

    Article  PubMed  Google Scholar 

  173. Walker, S. S. & Black, T. A. Are outer-membrane targets the solution for MDR Gram-negative bacteria? Drug Discov. Today 26, 2152–2158 (2021).

    Article  CAS  PubMed  Google Scholar 

  174. Naclerio, G. A. & Sintim, H. O. Multiple ways to kill bacteria via inhibiting novel cell wall or membrane targets. Future Med. Chem. 12, 1253–1279 (2020).

    Article  CAS  PubMed  Google Scholar 

  175. Hart, E. M. et al. A small-molecule inhibitor of BamA impervious to efflux and the outer membrane permeability barrier. Proc. Natl Acad. Sci. USA 116, 21748–21757 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  176. Imai, Y. et al. A new antibiotic selectively kills Gram-negative pathogens. Nature 576, 459–464 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  177. Kaur, H. et al. The antibiotic darobactin mimics a β-strand to inhibit outer membrane insertase. Nature 593, 125–129 (2021).

    Article  CAS  PubMed  Google Scholar 

  178. Ritzmann, N., Manioglu, S., Hiller, S. & Müller, D. J. Monitoring the antibiotic darobactin modulating the β-barrel assembly factor BamA. Structure 30, 350–359.e3 (2022).

    Article  CAS  PubMed  Google Scholar 

  179. Steenhuis, M. et al. Inhibition of autotransporter biogenesis by small molecules. Mol. Microbiol. 112, 81–98 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  180. Urfer, M. et al. A peptidomimetic antibiotic targets outer membrane proteins and disrupts selectively the outer membrane in Escherichia coli. J. Biol. Chem. 291, 1921–1932 (2016).

    Article  CAS  PubMed  Google Scholar 

  181. Luther, A. et al. Chimeric peptidomimetic antibiotics against Gram-negative bacteria. Nature 576, 452–458 (2019).

    Article  CAS  PubMed  Google Scholar 

  182. Schulz, G. E. The structure of bacterial outer membrane proteins. Biochim. Biophys. Acta 1565, 308–317 (2002).

    Article  CAS  PubMed  Google Scholar 

  183. Acosta-Gutiérrez, S., Scorciapino, M. A., Bodrenko, I. & Ceccarelli, M. Filtering with electric field: the case of E. coli porins. J. Phys. Chem. Lett. 6, 1807–1812 (2015).

    Article  PubMed  Google Scholar 

  184. Acosta-Gutiérrez, S. et al. Getting drugs into Gram-negative bacteria: rational rules for permeation through general porins. ACS Infect. Dis. 4, 1487–1498 (2018).

    Article  PubMed  Google Scholar 

  185. Noinaj, N. et al. Structural insight into the biogenesis of β-barrel membrane proteins. Nature 501, 385–390 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  186. Iadanza, M. G. et al. Distortion of the bilayer and dynamics of the BAM complex in lipid nanodiscs. Commun. Biol. 3, 766 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  187. Wu, R. et al. Plasticity within the barrel domain of BamA mediates a hybrid-barrel mechanism by BAM. Nat. Commun. 12, 7131 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  188. Bakelar, J., Buchanan, S. K. & Noinaj, N. The structure of the β-barrel assembly machinery complex. Science 351, 180–186 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  189. Gu, Y. et al. Structural basis of outer membrane protein insertion by the BAM complex. Nature 531, 64–69 (2016).

    Article  CAS  PubMed  Google Scholar 

  190. Han, L. et al. Structure of the BAM complex and its implications for biogenesis of outer-membrane proteins. Nat. Struct. Mol. Biol. 23, 192–196 (2016).

    Article  CAS  PubMed  Google Scholar 

  191. Iadanza, M. G. et al. Lateral opening in the intact β-barrel assembly machinery captured by cryo-EM. Nat. Commun. 7, 12865 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  192. Tomasek, D. et al. Structure of a nascent membrane protein as it folds on the BAM complex. Nature 583, 473–478 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  193. Łapińska, U. et al. Fast bacterial growth reduces antibiotic accumulation and efficacy. eLife https://doi.org/10.7554/eLife.74062 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  194. Toyofuku, M., Nomura, N. & Eberl, L. Types and origins of bacterial membrane vesicles. Nat. Rev. Microbiol. 17, 13–24 (2019).

    Article  CAS  PubMed  Google Scholar 

  195. Dhital, S., Deo, P., Stuart, I. & Naderer, T. Bacterial outer membrane vesicles and host cell death signaling. Trends Microbiol. 29, 1106–1116 (2021).

    Article  CAS  PubMed  Google Scholar 

  196. Sartorio, M. G., Pardue, E. J., Feldman, M. F. & Haurat, M. F. Bacterial outer membrane vesicles: from discovery to applications. Annu. Rev. Microbiol. 75, 609–630 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  197. Kadurugamuwa, J. L. & Beveridge, T. J. Virulence factors are released from Pseudomonas aeruginosa in association with membrane vesicles during normal growth and exposure to gentamicin: a novel mechanism of enzyme secretion. J. Bacteriol. 177, 3998–4008 (1995).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  198. Haurat, M. F., Elhenawy, W. & Feldman, M. F. Prokaryotic membrane vesicles: new insights on biogenesis and biological roles. Biol. Chem. 396, 95–109 (2015).

    Article  CAS  PubMed  Google Scholar 

  199. Samsudin, F., Boags, A., Piggot, T. J. & Khalid, S. Braun’s lipoprotein facilitates OmpA interaction with the Escherichia coli cell wall. Biophys. J. 113, 1496–1504 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  200. Beeby, M. Toward organism-scale structural biology: S-layer reined in by bacterial LPS. Trends Biochem. Sci. 45, 549–551 (2020).

    Article  CAS  PubMed  Google Scholar 

  201. Bharat, T. A. M., von Kugelgen, A. & Alva, V. Molecular logic of Prokaryotic surface layer structures. Trends Microbiol. 29, 405–415 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  202. Liston, S. D. & Willis, L. M. Racing to build a wall: glycoconjugate assembly in Gram-positive and Gram-negative bacteria. Curr. Opin. Struct. Biol. 68, 55–65 (2021).

    Article  CAS  PubMed  Google Scholar 

  203. Phanphak, S. et al. Super-resolution fluorescence microscopy study of the production of K1 capsules by Escherichia coli: evidence for the differential distribution of the capsule at the poles and the equator of the cell. Langmuir 35, 5635–5646 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  204. Yin, J. et al. Genetically encoded short peptide tag for versatile protein labeling by Sfp phosphopantetheinyl transferase. Proc. Natl Acad. Sci. USA 102, 15815–15820 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  205. Matias, V. R., Al-Amoudi, A., Dubochet, J. & Beveridge, T. J. Cryo-transmission electron microscopy of frozen-hydrated sections of Escherichia coli and Pseudomonas aeruginosa. J. Bacteriol. 185, 6112–6118 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  206. Okuda, S., Sherman, D. J., Silhavy, T. J., Ruiz, N. & Kahne, D. Lipopolysaccharide transport and assembly at the outer membrane: the PEZ model. Nat. Rev. Microbiol. 14, 337–345 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  207. Shu, W., Liu, J., Ji, H. & Lu, M. Core structure of the outer membrane lipoprotein from Escherichia coli at 1.9Å resolution. J. Mol. Biol. 299, 1101–1112 (2000).

    Article  CAS  PubMed  Google Scholar 

  208. Braun, V. & Rehn, K. Chemical characterization, spatial distribution and function of a lipoprotein (murein-lipoprotein) of the E. coli cell wall. The specific effect of trypsin on the membrane structure. Eur. J. Biochem. 10, 426–438 (1969).

    Article  CAS  PubMed  Google Scholar 

  209. Khalid, S., Piggot, T. J. & Samsudin, F. Atomistic and coarse grain simulations of the cell envelope of Gram-negative bacteria: what have we learned? Acc. Chem. Res. 52, 180–188 (2019).

    Article  CAS  PubMed  Google Scholar 

  210. Gruss, F. et al. The structural basis of autotransporter translocation by TamA. Nat. Struct. Mol. Biol. 20, 1318–1320 (2013).

    Article  CAS  PubMed  Google Scholar 

  211. Ruiz, N., Davis, R. M. & Kumar, S. YhdP, TamB, and YdbH are redundant but essential for growth and lipid homeostasis of the Gram-negative outer membrane. mBio 12, e0271421 (2021).

    Article  PubMed  Google Scholar 

  212. Ding, Y. et al. Characterization of BamA reconstituted into a solid-supported lipid bilayer as a platform for measuring dynamics during substrate protein assembly into the membrane. Biochim. Biophys. Acta Biomembr. 1862, 183317 (2020).

    Article  CAS  PubMed  Google Scholar 

  213. Chen, X. et al. Substrate-dependent arrangements of the subunits of the BAM complex determined by neutron reflectometry. Biochim. Biophys. Acta Biomembr. 1863, 183587 (2021).

    Article  CAS  PubMed  Google Scholar 

  214. Beveridge, T. J. & Davies, J. A. Cellular responses of Bacillus subtilis and Escherichia coli to the Gram stain. J. Bacteriol. 156, 846–858 (1983).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  215. Davies, J. A., Anderson, G. K., Beveridge, T. J. & Clark, H. C. Chemical mechanism of the Gram stain and synthesis of a new electron-opaque marker for electron microscopy which replaces the iodine mordant of the stain. J. Bacteriol. 156, 837–845 (1983).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  216. Hernández, S. B. & Cava, F. New approaches and techniques for bacterial cell wall analysis. Curr. Opin. Microbiol. 60, 88–95 (2021).

    Article  PubMed  Google Scholar 

  217. Viljoen, A., Foster, S. J., Fantner, G. E., Hobbs, J. K. & Dufrêne, Y. F. Scratching the surface: bacterial cell envelopes at the nanoscale. mBio https://doi.org/10.1128/mBio.03020-19 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  218. Touhami, A., Jericho, M. H. & Beveridge, T. J. Atomic force microscopy of cell growth and division in Staphylococcus aureus. J. Bacteriol. 186, 3286–3295 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  219. Andre, G. et al. Imaging the nanoscale organization of peptidoglycan in living Lactococcus lactis cells. Nat. Commun. 1, 27 (2010).

    Article  PubMed  Google Scholar 

  220. Turner, R. D. et al. Peptidoglycan architecture can specify division planes in Staphylococcus aureus. Nat. Commun. 1, 26 (2010).

    Article  PubMed  Google Scholar 

  221. Dover, R. S., Bitler, A., Shimoni, E., Trieu-Cuot, P. & Shai, Y. Multiparametric AFM reveals turgor-responsive net-like peptidoglycan architecture in live streptococci. Nat. Commun. 6, 7193 (2015).

    Article  PubMed  Google Scholar 

  222. Gustafsson, M. G. Nonlinear structured-illumination microscopy: wide-field fluorescence imaging with theoretically unlimited resolution. Proc. Natl Acad. Sci. USA 102, 13081–13086 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  223. Betzig, E. et al. Imaging intracellular fluorescent proteins at nanometer resolution. Science 313, 1642–1645 (2006).

    Article  CAS  PubMed  Google Scholar 

  224. Gaboriaud, F., Bailet, S., Dague, E. & Jorand, F. Surface structure and nanomechanical properties of Shewanella putrefaciens bacteria at two pH values (4 and 10) determined by atomic force microscopy. J. Bacteriol. 187, 3864–3868 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  225. Gaboriaud, F., Parcha, B. S., Gee, M. L., Holden, J. A. & Strugnell, R. A. Spatially resolved force spectroscopy of bacterial surfaces using force-volume imaging. Colloids Surf. B Biointerfaces 62, 206–213 (2008).

    Article  CAS  PubMed  Google Scholar 

  226. Dufrêne, Y. F., Viljoen, A., Mignolet, J. & Mathelié-Guinlet, M. AFM in cellular and molecular microbiology. Cell Microbiol. 23, e13324 (2021).

    Article  PubMed  Google Scholar 

  227. Plomp, M., Leighton, T. J., Wheeler, K. E., Hill, H. D. & Malkin, A. J. In vitro high-resolution structural dynamics of single germinating bacterial spores. Proc. Natl Acad. Sci. USA 104, 9644–9649 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  228. Wang, H., Wilksch, J. J., Lithgow, T., Strugnell, R. A. & Gee, M. L. Nanomechanics measurements of live bacteria reveal a mechanism for bacterial cell protection: the polysaccharide capsule in Klebsiella is a responsive polymer hydrogel that adapts to osmotic stress. Soft Matter 9, 7560–7567 (2013).

    Article  CAS  Google Scholar 

  229. Fantner, G. E., Barbero, R. J., Gray, D. S. & Belcher, A. M. Kinetics of antimicrobial peptide activity measured on individual bacterial cells using high-speed atomic force microscopy. Nat. Nanotechnol. 5, 280–285 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  230. Raman, A. et al. Mapping nanomechanical properties of live cells using multi-harmonic atomic force microscopy. Nat. Nanotechnol. 6, 809–814 (2011).

    Article  CAS  PubMed  Google Scholar 

  231. Konovalova, A., Kahne, D. E. & Silhavy, T. J. Outer membrane biogenesis. Annu. Rev. Microbiol. 71, 539–556 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  232. Ranava, D., Caumont-Sarcos, A., Albenne, C. & Ieva, R. Bacterial machineries for the assembly of membrane-embedded β-barrel proteins. FEMS Microbiol. Lett. https://doi.org/10.1093/femsle/fny087 (2018).

    Article  PubMed  Google Scholar 

  233. Albenne, C. & Ieva, R. Job contenders: roles of the β-barrel assembly machinery and the translocation and assembly module in autotransporter secretion. Mol. Microbiol. 106, 505–517 (2017).

    Article  CAS  PubMed  Google Scholar 

  234. Wu, R., Stephenson, R., Gichaba, A. & Noinaj, N. The big BAM theory: an open and closed case? Biochim. Biophys. Acta Biomembr. 1862, 183062 (2020).

    Article  CAS  PubMed  Google Scholar 

  235. Tomasek, D. & Kahne, D. The assembly of β-barrel outer membrane proteins. Curr. Opin. Microbiol. 60, 16–23 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  236. Anwari, K. et al. The evolution of new lipoprotein subunits of the bacterial outer membrane BAM complex. Mol. Microbiol. 84, 832–844 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  237. Webb, C. T., Heinz, E. & Lithgow, T. Evolution of the β-barrel assembly machinery. Trends Microbiol. 20, 612–620 (2012).

    Article  CAS  PubMed  Google Scholar 

  238. Stubenrauch, C., Grinter, R. & Lithgow, T. The modular nature of the β-barrel assembly machinery, illustrated in Borrelia burgdorferi. Mol. Microbiol. 102, 753–756 (2016).

    Article  CAS  PubMed  Google Scholar 

  239. Stubenrauch, C. J. & Lithgow, T. The TAM: a translocation and assembly module of the β-barrel assembly machinery in bacterial outer membranes. EcoSal https://doi.org/10.1128/ecosalplus.ESP-0036-2018 (2019).

    Article  Google Scholar 

  240. Sandoval, C. M., Baker, S. L., Jansen, K., Metzner, S. I. & Sousa, M. C. Crystal structure of BamD: an essential component of the β-barrel assembly machinery of Gram-negative bacteria. J. Mol. Biol. 409, 348–357 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

Work in this area in the authors’ laboratories is supported by the Australian Research Council. The authors thank their colleagues Rebecca Bamert and Iain Hay for insightful comments on the manuscript.

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Authors and Affiliations

  1. Centre to Impact AMR, Monash University, Clayton, Victoria, Australia

    Trevor Lithgow & Christopher J. Stubenrauch

  2. Infection Program, Biomedicine Discovery Institute and Department of Microbiology, Monash University, Clayton, Victoria, Australia

    Trevor Lithgow & Christopher J. Stubenrauch

  3. School of BioSciences and School of Mathematics and Statistics, The University of Melbourne, Parkville, Victoria, Australia

    Michael P. H. Stumpf

Authors
  1. Trevor Lithgow
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  3. Michael P. H. Stumpf
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T.L. initially reviewed the literature in the field. All authors contributed to further review, writing and other aspects of the article.

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Correspondence to Trevor Lithgow.

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Nature Reviews Microbiology thanks Susan Buchanan, who co-reviewed with Kathryn Diederichs, Kim Lewis and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Glossary

β-barrel assembly precincts

Functionally defined as the set of β-barrel assembly machinery complexes shown to be in close proximity.

β-barrel islands

Areas of β-barrel proteins 500 nm or more in diameter as observed in total internal reflection fluorescence microscopy (TIRFM) imaging of Escherichia coli.

β-barrel protein arrays

Extensive areas of the outer membrane formed from β-barrel proteins.

β-barrel proteins

Proteins embedded within the outer membrane of Gram-negative bacteria; the transmembrane region consists of a β-barrel, which is an anti-parallel β-sheet twisted into a cylinder in which the first and last β-strands are stitched together through a strong hydrogen-bonding network.

Cellscape

A term we propose for the cellular equivalent to a landscape, for which the topographical details are surveyed and documented by nanoscale imaging tools such as atomic force microscopy, super-resolution microscopy and cryo-electron tomography and charted by nanoscale cartography as a 3D map of the cell surface.

Lipopolysaccharide

(LPS). A lipid A species with multiple acyl chains, conjugated to an inner and outer core oligosaccharide (which is the rough LPS seen in some bacteria), onto which an O-antigen polysaccharide is attached (this O-antigen can be of variable sugar composition); phospholipids are present in bacterial outer membranes, but only in the inner leaflet.

Lipoprotein

A portmanteau of ‘lipid’ and ‘protein’; these molecules are triacylated at the essential N-terminal cysteine residue and are typically embedded within the periplasmic face of the inner or outer membrane, but some lipoproteins such as BamC and RcsF (in Escherichia coli) are surface-exposed.

LOL pathway

A localisation of lipoprotein (LOL) pathway responsible for the transport of lipoproteins from the inner membrane to the outer membrane.

LPS patches

Discrete patches of Escherichia coli outer membrane occupied by lipopolysaccharide (LPS); LPS patches range in size from 25 nm to 225 nm in diameter (mean diameter of 55 nm), with each LPS patch being surrounded at its periphery by β-barrel proteins.

LPS translocase

A translocase situated in the outer membrane and composed of the β-barrel protein LptD and lipoprotein LptE; the lipopolysaccharide (LPS) translocase is responsible for flipping newly arrived molecules of LPS from the inner leaflet to the outer leaflet of the outer membrane.

Outer membrane vesicles

(OMVs). Vesicles formed by evagination of the outer membrane; the formation of OMVs requires factors that induce local regions of curvature in the outer membrane, and the OMVs once formed consist of a lipopolysaccharide-rich, phospholipid-rich shell that also has outer membrane proteins incorporated.

Sec translocon

The major protein translocation channel in the inner membrane of bacteria, where entry of a substrate protein into the Sec translocon depends on an N-terminal signal sequence.

Transertion

A concept developed to explain the spatial restriction of inner membrane protein assembly, through the regulated and tight coupling of transcription, translation and insertion of membrane proteins.

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Lithgow, T., Stubenrauch, C.J. & Stumpf, M.P.H. Surveying membrane landscapes: a new look at the bacterial cell surface. Nat Rev Microbiol 21, 502–518 (2023). https://doi.org/10.1038/s41579-023-00862-w

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