Download Editorial: The many wonders of the bacterial cell surface

FEMS Microbiology Reviews, fuv047, 40, 2016, 161–163
doi: 10.1093/femsre/fuv047
Advance Access Publication Date: 17 December 2015
Editorial
Editorial: The many wonders of the bacterial cell surface
The microbial world offers constant reminders of the astonishing and exquisite complexity of unicellular life. The bacterial
cell envelope is a remarkable example of a multifunctional and
multi-faceted structure designed to protect both the integrity
of the cell and dictate its shape. It insulates the intracellular
compartment from the outside world but still preserves a phenomenal ability to communicate and sense the extracellular environment and exerts control of molecular trafficking of a vast
array of nutrients and macromolecules. A virtual issue proposed
by FEMS Microbiology Reviews, and entitled ‘Bacterial Cell Surfaces’, provides an exciting flight over the principle features of
the composition, flexibility and function of the bacterial cell
envelope.
Glycerophospholipids represent a basic constituent of all
membranes. They form the membrane bilayer that immediately
surrounds the bacterial cytoplasmic compartment, as well as
the inner leaflet of the Gram-negative outer membrane. While
it has long been believed that the membrane composition is relatively fixed, Sohlenkamp and Geiger present a remarkable illustration of the variability of phospholipid content between different species and within a single species faced with the need to
adapt to changing environments (Sohlenkamp and Geiger 2015).
One of the defining features of bacteria is the application of
peptidoglycan (PG) to create the rigid, stress-bearing layer of the
cell envelope and dictate cell shape. This is a thick multi-layered
structure in Gram-positive bacteria but is predominantly singlelayered in Gram-negative bacteria, which have the added protection afforded by the outer membrane. Despite the wide distribution of PG, a few controversial exceptions have remained where
this macromolecule could not be identified with conventional
methods. Chlamydia-related bacteria provide a classic example. In their review, Jacquier and colleagues report on extraordinary advances that have finally resolved the question of whether
Chlamydia-related bacteria contain PG. Not only is PG present,
it is also crucial in cell division and for the proper assembly of
the septum (Jacquier et al. 2015).
As mentioned above, Gram-negative bacteria contain a characteristic outer membrane, which is an asymmetric bilayer containing phospholipids at the inner leaflet and lipopolysaccharides (LPS) in the outer leaflet and covering ∼75% of the cell
surface. The placement of molecules at the surface creates a
substantial challenge for bacteria, where the source of activated building blocks is confined to the cytoplasm and cytoplasmic membrane. An extensive literature describes trafficking of
outer membrane and extracellular proteins (see below), but the
mechanisms underpinning the delivery of phospholipids and
LPS have been enigmatic. However, recent research has offered
detailed insight into the transport of LPS. The review by Putker
and colleagues takes us into a trip across the cell envelope where
the structural regions of LPS are synthesized (beginning at the
interface of the cytosol and the inner membrane) before being
flipped to the periplasm by dedicated transporters. Once assembled a remarkably efficient envelope-spanning molecular machine (the Lpt system) delivers the new molecules to the cell surface (Putker, Bos and Tommassen 2015). The complexity of the
structure of LPS is matched by complexity in the assembly pathways. The O-antigen polysaccharide portion of LPS is assembled
independently of the lipid A-core domain and the two parts are
joined before their entry into the Lpt translocation machine. Kalynych and colleagues provide a historical perspective leading to
our current understanding of the molecular details of O-antigen
formation (Kalynych et al. 2014).
Being at the very immediate interface with the external environment, LPS is one of the key molecules detected by the host
and serves as a pivotal signaling molecule in a pathogen’s interaction with the innate and acquired immune systems. Unlike the more conserved lipid A, the distal O-antigens are hypervariable due to a remarkable range of structural diversity.
These molecules have been exploited for valuable serotyping
strategies and may provide a significant advantage to the bacterial pathogen, as discussed for Salmonella in our virtual issue
(Liu et al. 2014). Many bacteria, both Gram-negative and
Gram-positive, use capsular polysaccharides to evade host defenses. While these polymers are hypervariable, like O antigens, some have the added advantage of being poorly- or nonimmunogenic. This fascinating aspect is described by Cress and
colleagues as ‘Masquerading microbial pathogens’ (Cress et al.
2014). In many cases bacteria do not live as isolated organisms
immediately accessible to the immune system, but instead creates communities called biofilms, which are encased in a matrix
containing exopolysaccharides and other molecules that glue
the community onto a surface. The role of cell surface macromolecules in establishing the 3D-architecture of biofilms is also
reviewed in this virtual issue (Hobley et al. 2015).
It is also important to recognize that polysaccharides are not
the only type of molecules that dominate the bacterial surface.
Proteins and glycoproteins can also create structures called Slayers, which cover the cell surface. These possess protective
properties but also play roles in virulence and adherence. The
functions and mechanisms of assembly/insertion of this family of proteins in bacteria and archaea are superbly described in
a review by Sleytr and colleagues and collated within the virtual issue ‘Bacterial Cell Surfaces’ (Sleytr et al. 2014). Whereas
the S-layer proteins in bacteria are mostly anchored to the PG
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FEMS Microbiology Reviews, 2016, Vol. 40, No. 2
Figure 1. Schematic representation of the cell envelope of gram-positive (left) and gram-negative (right) bacteria. Some elements of the envelope have been labelled.
The cytoplasmic membrane (CM) and inner leaflet of the outer membrane (OM) in gram-negative bacterium are made of phospholipids while the outer leaflet of the OM
is mainly LPS (core LPS in green). Grey shapes within membranes are mostly integral membrane proteins or lipoproteins. As examples macromolecular complexes have
been represented attached to or inserted in the cell envelope such as pili (red in gram-positive) or type III secretion system (needle-like structure in gram-negative).
or attached to LPS, some archaea have lipoprotein S-layers that
are anchored through their fatty acyl chains into the lipid bilayer. It has become quite obvious that lipidation of proteins
is a widespread strategy to anchor certain classes of membrane proteins. It provides an alternative (but equally important)
approach to the standard integral inner membrane proteins
with their hydrophobic transmembrane domains, or the outer
membrane barrel proteins built of amphipathic beta-strands or
alpha-helices. Dedicated machineries can deliver lipoproteins
to any location in the cell envelope (i.e. inner membrane, outer
membrane inner leaflet or exposed at the cell surface) where
they exert a variety of roles including in cell envelope homeostasis. The enzymology of protein lipidation and the export pathway for lipoproteins are comprehensively described in a review
by Nienke Buddelmeijer (Buddelmeijer 2015).
Bacteria assemble complex cell surface structures to achieve
a broad range of basic but essential functions. A variety of fascinating and complex protein-based structures have evolved to
meet these requirements. Some bacteria need to attach or move
on a surface and can, for example, use type IV pili (Berry and
Pelicic 2015). Others exchange genetic material and use conjugative pili and related type IV secretion systems (T4SSs) (Cabezón
et al. 2015). Some bacteria have lifestyles dependent on the ability to inject effector and toxins into target cells to subvert the
host and take advantage during the colonization process and
can use the type III secretion system (T3SS) to fulfill such purposes (Diepold and Wagner 2014). In all cases, the proteinaceous structures contain a portion that resembles a filament
or a needle that emerges from the cell surface and is made of
only few different subunits. However, the molecular platform
that facilitates the assembly of the filament/needle is a sophisticated supra-molecular machine inserted in the cell envelope.
In the case of Gram-negative bacteria, this machine spans both
inner and outer membranes. After decades of progress in experimental tools, particularly X-ray crystallography and cryoelectron microscopy, these machines have now been visualized
at high resolution. The emerging images illustrate a level of complexity and functional sophistication that we could not have
imagined. The molecular details of these trafficking systems, in-
cluding all the current protein secretion systems (e.g. T1SS to
T7SS), have been investigated and revealed in many bacteria,
but understanding their counterparts in some other bacteria is
still in its infancy. Nevertheless, the massive amount of foundational information now makes possible to browse the genome
of a less tractable organism, such as the intracellular bacterium
Rickettsia, to identify its secretome – its putative composition in
terms of secretion systems and secreted proteins (Gillespie et al.
2015).
Our understanding of the bacterial cell envelope has been
advanced by the impressive development of new experimental
methods, particularly those involving imaging and structural biology. However, new and emerging technologies offer the potential to further illuminate bacterial surface composition and dynamics. One critical new approach called metabolic labeling allows researchers to specifically label a cellular component and
follow its history in time and space. An overview of the current state-of-the-art in this area is presented in our virtual issue, thanks to the review by Siegrist and colleagues, who discuss
the impact this approach had on studies concerning bacterial
growth, division and secretion (Siegrist et al. 2015).
Virtual issue
This paper will appear in the FEMS Reviews virtual issue, Bacterial Cell Surfaces, at http://femsre.oxfordjournals.org/content/
virtual-issue-bacterial-cell-surfaces.
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∗
Alain Filloux, Department of Life Sciences, MRC Centre for Molecular
Bacteriology and Infection, Imperial College London, South Kensington
Campus, London, SW7 2AZ, United Kingdom;
E-mail: [email protected]
∗
Chris Whitfield, Department of Molecular and Cellular Biology, University of Guelph, Guelph, ON, Canada N1G 2W1;
E-mail: [email protected]
∗
Corresponding editors.