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Chembiochem : a European Journal of... Apr 2023Serving as an exoskeletal scaffold, peptidoglycan is a polymeric macromolecule that is essential and conserved across all bacteria, yet is absent in mammalian cells;... (Review)
Review
Serving as an exoskeletal scaffold, peptidoglycan is a polymeric macromolecule that is essential and conserved across all bacteria, yet is absent in mammalian cells; this has made bacterial peptidoglycan a well-established excellent antibiotic target. In addition, soluble peptidoglycan fragments derived from bacteria are increasingly recognised as key signalling molecules in mediating diverse intra- and inter-species communication in nature, including in gut microbiota-host crosstalk. Each bacterial species encodes multiple redundant enzymes for key enzymatic activities involved in peptidoglycan assembly and breakdown. In this review, we discuss recent findings on the biochemical activities of major peptidoglycan enzymes, including peptidoglycan glycosyltransferases (PGT) and transpeptidases (TPs) in the final stage of peptidoglycan assembly, as well as peptidoglycan glycosidases, lytic transglycosylase (LTs), amidases, endopeptidases (EPs) and carboxypeptidases (CPs) in peptidoglycan turnover and metabolism. Biochemical characterisation of these enzymes provides valuable insights into their substrate specificity, regulation mechanisms and potential modes of inhibition.
Topics: Peptidoglycan; Bacteria; Glycosyltransferases; Cell Wall; Substrate Specificity; Bacterial Proteins
PubMed: 36715567
DOI: 10.1002/cbic.202200693 -
Biochimie Dec 2022The objective of the present review is to provide an insight into modifications of microbial cell walls and membrane constituents by using the aminoacyl-tRNA as amino... (Review)
Review
The objective of the present review is to provide an insight into modifications of microbial cell walls and membrane constituents by using the aminoacyl-tRNA as amino acid donor. In bacteria, phospholipids are modified by Multiple peptide resistance Factor enzymes and peptidoglycan precursors by so called fem ligases. Although these modifications were thought to be restricted to procaryotes, we discovered enzymes that modify ergosterol (the main component of fungal membrane) with glycine and aspartate. The focus of this review is to present the molecular mechanisms underlying all these processes together with the structure of the enzymes and their substrates. This article also reviews how substrates are recognized and modified and how the products are subsequently exported in various organisms. Finally, the physiological outcome and the discoveries of each family of enzymes is also discussed.
Topics: Amino Acids; RNA, Transfer; Cell Wall; RNA, Transfer, Amino Acyl; Peptidoglycan; Amino Acyl-tRNA Synthetases
PubMed: 36184002
DOI: 10.1016/j.biochi.2022.09.017 -
Current Biology : CB Apr 2018To determine the fundamentals of cell growth, we must extend cell biological studies to non-model organisms. Here, we investigated the growth modes of the only two rods...
To determine the fundamentals of cell growth, we must extend cell biological studies to non-model organisms. Here, we investigated the growth modes of the only two rods known to widen instead of elongating, Candidatus Thiosymbion oneisti and Thiosymbion hypermnestrae. These bacteria are attached by one pole to the surface of their respective nematode hosts. By incubating live Ca. T. oneisti and T. hypermnestrae with a peptidoglycan metabolic probe, we observed that the insertion of new cell wall starts at the poles and proceeds inward, concomitantly with FtsZ-based membrane constriction. Remarkably, in Ca. T. hypermnestrae, the proximal, animal-attached pole grows before the distal, free pole, indicating that the peptidoglycan synthesis machinery is host oriented. Immunostaining of the symbionts with an antibody against the actin homolog MreB revealed that it was arranged medially-that is, parallel to the cell long axis-throughout the symbiont life cycle. Given that depolymerization of MreB abolished newly synthesized peptidoglycan insertion and impaired divisome assembly, we conclude that MreB function is required for symbiont widening and division. In conclusion, our data invoke a reassessment of the localization and function of the bacterial actin homolog.
Topics: Alphaproteobacteria; Animals; Bacterial Proteins; Cell Wall; Nematoda; Peptidoglycan; Symbiosis
PubMed: 29576473
DOI: 10.1016/j.cub.2018.02.028 -
Molecular Microbiology Feb 2015
Topics: Bacteriology; Germany; Glycosyltransferases; History, 20th Century; History, 21st Century; Penicillins; Peptidoglycan
PubMed: 25676688
DOI: 10.1111/mmi.12881 -
Biochimica Et Biophysica Acta Aug 2014Signal peptide-driven secretion of precursor proteins directs polypeptides across the plasma membrane of bacteria. Two pathways, Sec- and SRP-dependent, converge at the... (Review)
Review
Signal peptide-driven secretion of precursor proteins directs polypeptides across the plasma membrane of bacteria. Two pathways, Sec- and SRP-dependent, converge at the SecYEG translocon to thread unfolded precursor proteins across the membrane, whereas folded preproteins are routed via the Tat secretion pathway. Gram-positive bacteria lack an outer membrane and are surrounded by a rigid layer of peptidoglycan. Interactions with their environment are mediated by proteins that are retained in the cell wall, often through covalent attachment to the peptidoglycan. In this review, we describe the mechanisms for both Sec-dependent secretion and sortase-dependent assembly of proteins in the envelope of Gram-positive bacteria. This article is part of a Special Issue entitled: Protein trafficking and secretion in bacteria. Guest Editors: Anastassios Economou and Ross Dalbey.
Topics: Aminoacyltransferases; Bacterial Proteins; Cell Membrane; Cell Wall; Cysteine Endopeptidases; Gram-Positive Bacteria; Peptidoglycan; Protein Sorting Signals; Protein Transport
PubMed: 24269844
DOI: 10.1016/j.bbamcr.2013.11.009 -
STAR Protocols Mar 2022Postbiotics cooperate to influence immune and metabolic outcomes in the host. Here we describe a protocol for assessment of blood glucose control following acute...
Postbiotics cooperate to influence immune and metabolic outcomes in the host. Here we describe a protocol for assessment of blood glucose control following acute administration of lipopolysaccharide (LPS) and peptidoglycan (PGN) in mice. This protocol can be adapted for testing a broad range of microbial molecules and ligands for host immune receptors. Experience with mouse handling is required. For complete details on the use and execution of this protocol, please refer to Anhê et al. (2021) and Cavallari et al. (2017).
Topics: Animals; Cell Wall; Lipopolysaccharides; Mice; Peptidoglycan
PubMed: 35072117
DOI: 10.1016/j.xpro.2021.101098 -
Advances in Protein Chemistry and... 2022Gram-negative bacteria are surrounded by a complex multilayered cell envelope, consisting of an inner and an outer membrane, and separated by the aqueous periplasm,... (Review)
Review
Gram-negative bacteria are surrounded by a complex multilayered cell envelope, consisting of an inner and an outer membrane, and separated by the aqueous periplasm, which contains a thin peptidoglycan cell wall. These bacteria employ an arsenal of highly specialized membrane protein machineries to ensure the correct assembly and maintenance of the membranes forming the cell envelope. Here, we review the diverse protein systems, which perform these functions in Escherichia coli, such as the folding and insertion of membrane proteins, the transport of lipoproteins and lipopolysaccharide within the cell envelope, the targeting of phospholipids, and the regulation of mistargeted envelope components. Some of these protein machineries have been known for a long time, yet still hold surprises. Others have only recently been described and some are still missing pieces or yet remain to be discovered.
Topics: Cell Membrane; Cell Wall; Escherichia coli Proteins; Membrane Proteins; Peptidoglycan
PubMed: 35034716
DOI: 10.1016/bs.apcsb.2021.10.001 -
The Journal of Biological Chemistry Mar 2020Bacteria account for 1000-fold more biomass than humans. They vary widely in shape and size. The morphological diversity of bacteria is due largely to the different... (Review)
Review
Bacteria account for 1000-fold more biomass than humans. They vary widely in shape and size. The morphological diversity of bacteria is due largely to the different peptidoglycan-based cell wall structures that encase bacterial cells. Although the basic structure of peptidoglycan is highly conserved, consisting of long glycan strands that are cross-linked by short peptide chains, the mature cell wall is chemically diverse. Peptidoglycan hydrolases and cell wall-tailoring enzymes that regulate glycan strand length, the degree of cross-linking, and the addition of other modifications to peptidoglycan are central in determining the final architecture of the bacterial cell wall. Historically, it has been difficult to biochemically characterize these enzymes that act on peptidoglycan because suitable peptidoglycan substrates were inaccessible. In this review, we discuss fundamental aspects of bacterial cell wall synthesis, describe the regulation and diverse biochemical and functional activities of peptidoglycan hydrolases, and highlight recently developed methods to make and label defined peptidoglycan substrates. We also review how access to these substrates has now enabled biochemical studies that deepen our understanding of how bacterial cell wall enzymes cooperate to build a mature cell wall. Such improved understanding is critical to the development of new antibiotics that disrupt cell wall biogenesis, a process essential to the survival of bacteria.
Topics: Bacteria; Bacterial Proteins; Cell Wall; N-Acetylmuramoyl-L-alanine Amidase; Peptidoglycan; Protein Structure, Tertiary; Staphylococcus aureus; Substrate Specificity
PubMed: 31974163
DOI: 10.1074/jbc.REV119.010155 -
Biochemical Society Transactions Dec 2019Bacterial cell shape is a key trait governing the extracellular and intracellular factors of bacterial life. Rod-like cell shape appears to be original which implies... (Review)
Review
Bacterial cell shape is a key trait governing the extracellular and intracellular factors of bacterial life. Rod-like cell shape appears to be original which implies that the cell wall, division, and rod-like shape came together in ancient bacteria and that the myriad of shapes observed in extant bacteria have evolved from this ancestral shape. In order to understand its evolution, we must first understand how this trait is actively maintained through the construction and maintenance of the peptidoglycan cell wall. The proteins that are primarily responsible for cell shape are therefore the elements of the bacterial cytoskeleton, principally FtsZ, MreB, and the penicillin-binding proteins. MreB is particularly relevant in the transition between rod-like and spherical cell shape as it is often (but not always) lost early in the process. Here we will highlight what is known of this particular transition in cell shape and how it affects fitness before giving a brief perspective on what will be required in order to progress the field of cell shape evolution from a purely mechanistic discipline to one that has the perspective to both propose and to test reasonable hypotheses regarding the ecological drivers of cell shape change.
Topics: Bacteria; Bacterial Proteins; Biological Evolution; Cell Wall; Cytoskeleton; Peptidoglycan; RNA, Bacterial; RNA, Ribosomal, 16S
PubMed: 31829405
DOI: 10.1042/BST20180634 -
Current Opinion in Microbiology Apr 2021Synthesis of the bacterial cell envelope requires a regulated partitioning of resources from central metabolism. Here, we consider the key metabolic junctions that... (Review)
Review
Synthesis of the bacterial cell envelope requires a regulated partitioning of resources from central metabolism. Here, we consider the key metabolic junctions that provide the precursors needed to assemble the cell envelope. Peptidoglycan synthesis requires redirection of a glycolytic intermediate, fructose-6-phosphate, into aminosugar biosynthesis by the highly regulated branchpoint enzyme GlmS. MurA directs the downstream product, UDP-GlcNAc, specifically into peptidoglycan synthesis. Other shared resources required for cell envelope synthesis include the isoprenoid carrier lipid undecaprenyl phosphate and amino acids required for peptidoglycan cross-bridges. Assembly of the envelope requires a sharing of limited resources between competing cellular pathways and may additionally benefit from scavenging of metabolites released from neighboring cells or the formation of symbiotic relationships with a host.
Topics: Cell Membrane; Cell Wall; Peptidoglycan
PubMed: 33581378
DOI: 10.1016/j.mib.2021.01.015