Membranes are pivotal components of life. In an aqueous environment, these lipid bilayers form formidable insulators that demarcate the contained environment that forms a living cell, where biological processes can occur under controlled conditions. Membranes are such good insulators that they are a central player in biological energy generation in the form of ion gradients. As a further consequence, passage of ions, proteins, nucleic acids, nutrients and metabolites across membranes needs to be facilitated and requires an arsenal of dedicated channels and transporters. So does the transduction of signals and cues from the outside world into the cell and vice versa. In combination with supporting protein and glycan networks, membranes also provide shape and structure to cells and are important in cell motility. They further fulfil a scaffolding function for proteins and organelles exposed to the outside world and destined to interact with the extracellular environment. Clearly, a plethora of cellular processes evolve at and near cell membranes. In this book, the structural and molecular biology of these processes will be closer examined from a bacterial perspective.
In bacteria, two large groups can be identified based on the presence of either one or two lipid bilayers surrounding the cell. Historically these two groups have been referred to as, respectively, Gram-positive and Gram-negative bacteria based on their susceptibility or resistance to Gram staining. This staining indirectly reflects two different organizations of the cell envelope. In monoderm, or Gram-positive, bacteria the cell membrane is encapsulated by a thick layer of peptidoglycan, a network of cross-linked peptide and glycan units that provide shape and physical strength to the cell. In diderm or Gram-negative bacteria, a thin layer of peptidoglycan surrounds the cell membrane and is itself enclosed by a second lipid bilayer, the outer membrane. Both membranes have different protein and lipid composition and play specific roles. They enclose a cellular compartment referred to as the periplasmic space, that holds a dedicated repertoire of proteins but is devoid of nucleic acids or many of the metabolites associated with life. Additional layers such as two-dimensional protein arrays (or S-layers) and polysaccharide capsules are also present at the surface of many bacteria.
Many crucial processes are located at the cell envelope. Primarily, bacteria use this envelope as a protective layer from their hostile environment. S-layers and capsules protect bacteria from desiccation, low-pH, extracellular enzymes or virus infection. In both Gramnegative and Gram-positive bacteria, the rest of the cell envelope also plays a crucial role as a barrier around the cell. In both bacterial groups, the peptidoglycan layer shapes the cell and contributes to mechanical resistance of the cells. It is also directly involved in cell division. Because it is in contact with the outside world, this barrier is also an important interface. It selectively mediates the transport of molecules (solute and ions) and macromolecules (protein and DNA) in and out of the bacterial cell. Depending on the structure of their cell envelope, bacteria developed various systems to import and secrete molecules. These systems vary from individual channel or transporter proteins found in the bacterial inner- or outer membrane to complicated multiprotein complexes that span the entire cell envelope. Many surface appendages and adhesion proteins are also found at the surface of the bacteria. They are essential for bacterial survival by mediating cell motility, adhesion or various enzymatic activities. Their assembly or transport involves specialized systems, often related to secretion systems, located in bacterial cell envelope. Finally, bacteria developed sophisticated signal transduction systems at their surface to sense their environment or to communicate with their peers.
All these systems are essential for bacterial survival because they provide essential nutrients, help to bacteria to adapt quickly to changes in their environment or to live within bacterial communities. In addition, many pathogenic bacteria rely on these systems to infect their host. For example, many adhesion proteins or complexes that are displayed at the surface of the bacterial cell promote adhesion to and invasion of the host cell. The polysaccharide capsule or some enzymes exposed at the surface impair phagocytosis by the host during infection. Furthermore, given their central role in sustaining life, it should not surprise that membranes and membrane-associated processes form the subject of a series of antibacterial agents and molecules.
An impressive effort has been made by the microbiology community to understand the molecular details of the cell envelope, its biogenesis and function. In the recent years, some tremendous progresses have been obtained by a combination of molecular and structural biology approaches. In this book, specialists in the field present a selection of these recent progresses across the spectrum of the versatile functions and involvements of membranes in bacterial physiology. We are grateful to them for their valuable contributions.
Han Remaut and Rémi Fronzes
Part I Membrane Composition and Synthesis 1
1 Bacterial Cell Wall Growth, Shape and Division 3
Adeline Derouaux, Mohammed Terrak, Tanneke den Blaauwen and Waldemar Vollmer
2 The Outer Membrane of Gram-negative Bacteria: Lipopolysaccharide Biogenesis and Transport 55
Paola Sperandeo, Riccardo Villa, Gianni Dehò and Alessandra Polissi
3 Outer Membrane Protein Biosynthesis: Transport and Incorporation of Outer Membrane Proteins (in)to the Outer Membrane Bilayer 91
Kelly H. Kim, Suraaj Aulakh and Mark Paetzel
4 Bacterial Lipoproteins: Biogenesis, Virulence/ Pathogenicity and Trafficking 133
Hajime Tokuda, Peter Sander, Bok Luel Lee, Suguru Okuda, Thomas Grau, Andreas Tschumi, Juliane K. Brülle, Kenji Kurokawa and Hiroshi Nakayama
5 The Fascinating Coat Surrounding Mycobacteria 179
Mamadou Daffé and Benoît Zuber
Part II Protein–Lipid Interactions 193
6 The Role of Lipid Composition on Bacterial Membrane Protein Conformation and Function 195
Vinciane Grimard, Marc Lensink, Fabien Debailleul, Jean-Marie Ruysschaert and Cédric Govaerts
Part III Transport Across Bacterial Membranes 225
7 Bacterial ABC Transporters: Structure and Function 227
Anthony M. George and Peter M. Jones
8 Energy-coupled Transport Across the Outer Membrane of Gram-negative Bacteria 249
9 The Permeability Barrier: Passive and Active Drug Passage Across Membranes 283
Kozhinjampara R. Mahendran, Robert Schulz, Helge Weingart, Ulrich Kleinekathöfer and Mathias Winterhalter
10 Targeting and Integration of Bacterial Membrane Proteins 303
Patrick Kuhn, Renuka Kudva, Thomas Welte, Lukas Sturm and Hans-Georg Koch
11 Envelope-spanning Secretion Systems in Gram-negative Bacteria 343
Matthias J. Brunner, Rémi Fronzes and Thomas C. Marlovits
Part IV Signal Transduction Across Bacterial Membranes 385
12 Signalling Mechanisms in Prokaryotes 387
Mariano Martinez, Pedro M. Alzari and Gwénaëlle André-Leroux
Part V Bacterial Membranes in Pathogenesis 413
13 Outer Membrane-embedded and -associated Proteins and their Role in Adhesion and Pathogenesis 415
Vincent van Dam, Virginie Roussel-Jazédé, Jesús Arenas, Martine P. Bos and Jan Tommassen
14 Bacterial Membranes as Drug Targets 449
Alvin Lo, Gaetano Castaldo and Han Remaut