Bacterial Cell Wall Recycling

Abstract

Cell wall recycling is a process whereby bacteria degrade their own wall during growth, recover released constituents by active transport and reutilise them either to rebuild the wall or to gain energy. Most knowledge about cell wall recycling comes from studies with the Gram‐negative bacterium Escherichia coli . Within one generation, this organism breaks down and efficiently recycles approximately 60% of the mature peptidoglycan of its side‐wall during cell elongation and approximately 30% of newly deposited septal peptidoglycan during cell division. The reason for the massive turnover of the peptidoglycan is still unclear, although many other bacteria, including Gram‐positives, have been reported to turnover their cell wall and release similar quantities of peptidoglycan fragments during growth and differentiation. Whether these fragments are also recycled is basically unknown. The presence of recycling genes on most bacterial genomes, however, suggests that cell wall recycling is a very common pathway of bacteria. Key Concepts: The peptidoglycan of the bacterial cell wall represents a single, giant, reticular macromolecule (i.e. the murein sacculus) that encases the entire bacterial cell. The peptidoglycan cell wall has to be cleaved continuously during growth to allow cell expansion by insertion of new wall material. Bacteria possess a huge and partially redundant set of cell wall lytic enzymes that potentially target every covalent bond connecting the amino acid and amino sugar building blocks within the peptidoglycan network (cell wall lytic complement). Many bacteria release a great amount of cell wall material during bacterial growth (cell elongation and division). The reason for the massive turnover of approximately 50% of the existing peptidoglycan in one generation is still unclear. Bacteria eventually recover cell wall turnover fragments. The pathways for the continuous recycling of peptidoglycan have been explored in great detail in Escherichia coli . Cell wall recycling in Gram‐positive bacteria has been appreciated just recently and apparently differs from the E. coli paradigm as well as between Gram‐positive species. Cell wall‐derived peptidoglycan fragments function as potent biological effectors. They are involved in sensing the cell wall and growth state, inducing expression of antibiotic resistance genes, and triggering cell differentiation and resuscitation of dormant cells.

Peptidoglycan synthesis in Tannerella forsythia: Scavenging is the modus operandi

“…Generally, in bacteria about two‐thirds of peptidoglycan is degraded during cell wall turnover in cell division by lytic transglycosylases and endopeptidases, releasing GlcNAc‐1, 6‐anhydro‐MurNAc‐ l ‐Ala‐ d ‐Glu‐mesoDAP‐ d ‐Ala (anhydro‐muropeptide) as a major degradation product. In most Gram‐negative bacteria, the released muropeptides are then recycled into the cytoplasm via the AmpG‐like permeases . Orthologs of peptidoglycan recycling enzymes have been identified in some Gram‐positive bacteria as well, such as in Bacillus subtilis and Clostridium acetobutylicum .…”

“…In many Gram‐negative bacteria, but not E. coli , muropeptide fragments entering the cytoplasm due to cell wall damage or cell wall recycling regulate induction of chromosomal AmpC‐type β‐lactamases, which can provide resistance to β‐lactam antibiotics . For the purpose of peptidoglycan synthesis, after entering the cytoplasm, muropeptides are further broken down by amidases and carboxypeptidases to release GlcNAc, anhMurNAc, murein tripeptides and d ‐Ala, which then enter the peptidoglycan biosynthetic pathway . In the oral cavity, peptidoglycan fragments released from the cohabiting bacteria as a result of their cell wall turnover or death are expected to be available to T. forsythia .…”

“…In most Gram-negative bacteria, the released muropeptides are then recycled into the cytoplasm via the AmpG-like permeases. 6,27,28 Orthologs of peptidoglycan recycling enzymes have been identified in some Gram-positive bacteria as well, such as in Bacillus subtilis and Clostridium acetobutylicum. 34,36 In some bacteria, peptidoglycan fragments (muropeptides) function as important messengers in bacterial communication, and as antidormancy and spore resuscitation signals in some Gram-positive bacteria.…”

“…27 For the purpose of peptidoglycan synthesis, after entering the cytoplasm, muropeptides are further broken down by amidases and carboxypeptidases to release GlcNAc, anhMurNAc, murein tripeptides and d-Ala, which then enter the peptidoglycan biosynthetic pathway. 6,27,28 In the oral cavity, peptidoglycan fragments released from the cohabiting bacteria as a result of their cell wall turnover or death are expected to be available to T. forsythia. Importantly, scavenging on these fragments by T. forsythia is even more significant given that the human host does not make the peptidoglycan amino sugars.…”

Crystal Structure of the N-Acetylmuramic Acid α-1-Phosphate (MurNAc-α1-P) Uridylyltransferase MurU, a Minimal Sugar Nucleotidyltransferase and Potential Drug Target Enzyme in Gram-negative Pathogens

“…The bacterial peptidoglycan is a large, meshlike macromolecule consisting of polysaccharide chains of alternating N-acetylglucosamine (GlcNAc) and N-acetylmuramic acid (MurNAc) 4 links that are connected via short oligopeptide bridges (1). The biosynthesis of peptidoglycan is highly conserved and essential for bacteria, and enzymes within this synthetic pathway therefore represent attractive targets for antibacterial drug design.…”