The peptidoglycan layer is a unique and essential structural element in the cell wall of most bacteria (Peptidoglycan structure and architecture. FEMS Microbiology Reviews, 08 Jan 2008). Made of glycan strands cross-linked by short peptides, the so-called peptidoglycan sacculus forms a closed, bag-shaped structure surrounding the cytoplasmic membrane. Peptidoglycan sacculi have the strength to withstand the cell’s turgor pressure of up to 25 atmospheres. On the other hand, the sacculi are not rigid walls but are flexible structures, allowing reversible expansion under pressure, and they have relatively wide pores, enabling diffusion of large molecules such as proteins. Because the peptidoglycan completely surrounds the cytoplasmic membrane, the sacculus has a similar size and shape as the bacterial cells from which it was isolated.
The main function of peptidoglycan is to preserve cell integrity by withstanding the turgor pressure inside the cell. Inhibition of peptidoglycan biosynthesis (e.g. by mutations or antibiotics such as penicillin) or degradation (e.g. by lysozyme) in growing cells results in cell lysis. Peptidoglycan contributes to the maintenance of a defined cell shape (e.g. rod or sphere) and serves as a scaffold for anchoring other cell envelope components such as proteins and teichoic acids. It is intimately involved in the processes of cell growth and cell division. However, peptidoglycan is absent in some bacteria such as Mycoplasma species, Planctomyces, Rickettsia and Chlamidiae.
Peptidoglycan is composed of an overlapping lattice of two sugars, N-acetyl glucosamine (NAG) and N-acetyl muramic acid (NAM) cross-linked by amino acid bridges. The exact molecular makeup of these cross-bridges is species-specific. NAM is only found in the cell walls of bacteria and nowhere else. Attached to NAM is a side chain generally composed of four amino acids. In the best-studied bacterial cell wall (that of Esccherichia coli) the cross-bridge is most commonly composed of L-alanine, D-alanine, D-glutamic acid and diaminopimelic acid. In Staphylococcus aureus, the pentapeptide coming off the NAM is composed of the amino acids L-alanine, D-glutamine, L-lysine, and two D-alanines.
There is a two-layered organization of the bacterial cell wall, with a zone of low density next to the plasma membrane. This “inner wall zone” or “periplasmic space” has a thickness between 16 nm (in Staphylococcus aureus) and 22 nm (in Bacillus subtilis). The “outer wall zone” of higher density is the polymeric peptidoglycan–teichoic acid complex with its attached surface proteins. The thickness of the outer zone varies with the species, growth phase of the cells and growth conditions, but is in the range of 15–30 nm. Unravelling the molecular architecture of the bacterial cell wall has been a constant aspiration for microbiologists, but is proving to be a frustrating topic. In particular, the architecture of the cell wall of Gram-positive bacteria is far from being understood. Gram-positive species not only have a thick, multi-layered peptidoglycan but other major surface polymers linked to it.
The essential functions of peptidoglycan and its confinement to bacteria make it a perfect target for attacking these organisms. β-lactams and glycopeptides, powerful bactericidal antibiotics, interfere with the last steps of peptidoglycan synthesis. Glycopeptides such as vancomycin bind the C-terminal end of the peptidoglycan disaccharide-pentapeptide precursor, preventing its incorporation into peptidoglycan. The targets of β-lactams were identified as penicillin-binding proteins (PBPs), and multiple PBPs with different affinities for β-lactams are generally present in the cell envelope. Resistance to β-lactams is of major concern in the treatment of bacterial infections. Frequently, bacteria produce enzymes (β-lactamases) that inactivate these antibiotics. Gram-negative cells can reduce the permeability of their outer membrane and many bacteria lower the antibiotic concentration near the targets using efflux proteins. However, bacteria are also able to modify one or more important PBPs such that their affinity for the antibiotic is reduced, as is the case in peumococci. Methicillin resistant Staphylococcus aureus (MRSA) and Enterococci possess low affinity PBPs that replace the other PBPs in the presence of antibiotics. Resistance to glycopeptides was reported for the first time in enterococci in the 1980s. It results from the acquisition of genetic elements that allow the synthesis of modified peptidoglycan precursors showing a reduced binding capacity for the antibiotics. More recently, it was demonstrated that peptidoglycan has a role in innate immunity in mammals and insects and could contribute to bacterial pathogenesis.
In the last two decades, the improvement of analytical methods has shown that within a particular species, variations in peptidoglycan structure occur as a function of aging, growth medium, pathogenesis, or in the presence of antibiotics. This type of research has implications not only in the field of bacterial physiology, but also in those of innate immunity, pathogenicity, and antibacterial therapy.
- Getting bacteria into shape
- Cytoskeletal structure of Mycoplasma mobile
- Resuscitating Mycobacterium tuberculosis