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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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.
The authors declare no competing interests.
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- 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.
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.
(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.
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.
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 (2023). https://doi.org/10.1038/s41579-023-00862-w