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Molecules (Basel, Switzerland) Sep 2022Lysozymes are hydrolytic enzymes characterized by their ability to cleave the β-(1,4)-glycosidic bonds in peptidoglycan, a major structural component of the bacterial... (Review)
Review
Lysozymes are hydrolytic enzymes characterized by their ability to cleave the β-(1,4)-glycosidic bonds in peptidoglycan, a major structural component of the bacterial cell wall. This hydrolysis action compromises the integrity of the cell wall, causing the lysis of bacteria. For more than 80 years, its role of antibacterial defense in animals has been renowned, and it is also used as a preservative in foods and pharmaceuticals. In order to improve the antimicrobial efficacy of lysozyme, extensive research has been intended for its modifications. This manuscript reviews the natural antibiotic compound lysozyme with reference to its catalytic and non-catalytic mode of antibacterial action, lysozyme types, susceptibility and resistance of bacteria, modification of lysozyme molecules, and its applications in the food industry.
Topics: Animals; Anti-Bacterial Agents; Anti-Infective Agents; Antiviral Agents; Bacteria; Food Industry; Muramidase; Peptidoglycan; Pharmaceutical Preparations
PubMed: 36234848
DOI: 10.3390/molecules27196305 -
ELife Jan 2022The peptidoglycan cell wall is a predominant structure of bacteria, determining cell shape and supporting survival in diverse conditions. Peptidoglycan is dynamic and...
The peptidoglycan cell wall is a predominant structure of bacteria, determining cell shape and supporting survival in diverse conditions. Peptidoglycan is dynamic and requires regulated synthesis of new material, remodeling, and turnover - or autolysis - of old material. Despite exploitation of peptidoglycan synthesis as an antibiotic target, we lack a fundamental understanding of how peptidoglycan synthesis and autolysis intersect to maintain the cell wall. Here, we uncover a critical physiological role for a widely misunderstood class of autolytic enzymes, lytic transglycosylases (LTGs). We demonstrate that LTG activity is essential to survival by contributing to periplasmic processes upstream and independent of peptidoglycan recycling. Defects accumulate in LTG mutants due to generally inadequate LTG activity, rather than absence of specific enzymes, and essential LTG activities are likely independent of protein-protein interactions, as heterologous expression of a non-native LTG rescues growth of a conditional LTG-null mutant. Lastly, we demonstrate that soluble, uncrosslinked, endopeptidase-dependent peptidoglycan chains, also detected in the wild-type, are enriched in LTG mutants, and that LTG mutants are hypersusceptible to the production of diverse periplasmic polymers. Collectively, our results suggest that LTGs prevent toxic crowding of the periplasm with synthesis-derived peptidoglycan polymers and, contrary to prevailing models, that this autolytic function can be temporally separate from peptidoglycan synthesis.
Topics: Bacterial Proteins; Cell Wall; Endopeptidases; Peptidoglycan; Periplasm; Vibrio cholerae
PubMed: 35073258
DOI: 10.7554/eLife.73178 -
Chemical Reviews May 2022The peptidoglycan (PG) cell wall is an extra-cytoplasmic glycopeptide polymeric structure that protects bacteria from osmotic lysis and determines cellular shape. Since... (Review)
Review
The peptidoglycan (PG) cell wall is an extra-cytoplasmic glycopeptide polymeric structure that protects bacteria from osmotic lysis and determines cellular shape. Since the cell wall surrounds the cytoplasmic membrane, bacteria must add new material to the PG matrix during cell elongation and division. The lipid-linked precursor for PG biogenesis, Lipid II, is synthesized in the inner leaflet of the cytoplasmic membrane and is subsequently translocated across the bilayer so that the PG building block can be polymerized and cross-linked by complex multiprotein machines. This review focuses on major discoveries that have significantly changed our understanding of PG biogenesis in the past decade. In particular, we highlight progress made toward understanding the translocation of Lipid II across the cytoplasmic membrane by the MurJ flippase, as well as the recent discovery of a novel class of PG polymerases, the SEDS (shape, elongation, division, and sporulation) glycosyltransferases RodA and FtsW. Since PG biogenesis is an effective target of antibiotics, these recent developments may lead to the discovery of much-needed new classes of antibiotics to fight bacterial resistance.
Topics: Anti-Bacterial Agents; Bacteria; Bacterial Proteins; Cell Wall; Peptidoglycan; Polymerization; Uridine Diphosphate N-Acetylmuramic Acid
PubMed: 35274942
DOI: 10.1021/acs.chemrev.1c00773 -
Trends in Microbiology Jan 2019Fluorescent amino acid analogs have proven to be useful tools for studying the dynamics of peptidoglycan metabolism. García-Heredia and colleagues showed that their...
Fluorescent amino acid analogs have proven to be useful tools for studying the dynamics of peptidoglycan metabolism. García-Heredia and colleagues showed that their route of incorporation differs depending on the adjunct fluorophore and applied this property to investigate mycobacterial peptidoglycan synthesis and remodeling with heightened granularity.
Topics: Mycobacterium; Peptidoglycan
PubMed: 30497920
DOI: 10.1016/j.tim.2018.11.006 -
Cells Jan 2022Peptidoglycan recognition proteins (PGRPs) are key regulators in insects' immune response, functioning as sensors to detect invading pathogens and as scavengers of...
Peptidoglycan recognition proteins (PGRPs) are key regulators in insects' immune response, functioning as sensors to detect invading pathogens and as scavengers of peptidoglycan (PGN) to reduce immune overreaction. However, the exact function of PGRPs in is still unclear. In this study, we identified and functionally characterized the genes , and in . The results showed that , and all have an amidase-2 domain, which has been shown to have -Acetylmuramoyl-l-Alanine amidase activity. The transcriptional levels of and were both high in adult stages and midgut tissues; was found most abundantly expressed in the 2nd instar larvae stage and adult fat body. The expression of and and were significantly up-regulated after injury infected with at different time points; however, the expression of was reduced at 9 h, 24 h and 48 h following inoculation with . By injection of dsRNA, , and were knocked down by RNA-interference. Silencing of , and separately in flies resulted in over-activation of the Imd signaling pathway after bacterial challenge. The survival rate of the group was significantly reduced compared with the group after bacterial infection. Taken together, our results demonstrated that three catalytic family genes, , and , are important negative regulators of the Imd pathway in .
Topics: Bacterial Infections; Peptidoglycan; Signal Transduction
PubMed: 35011714
DOI: 10.3390/cells11010152 -
Viruses May 2018Peptidoglycan degrading enzymes are of increasing interest as antibacterial agents, especially against multi-drug resistant pathogens. Herein we present a review about... (Review)
Review
Peptidoglycan degrading enzymes are of increasing interest as antibacterial agents, especially against multi-drug resistant pathogens. Herein we present a review about the biological features of virion-associated lysins and endolysins, phage-derived enzymes that have naturally evolved to compromise the bacterial peptidoglycan from without and from within, respectively. These natural features may determine the adaptability of the enzymes to kill bacteria in different environments. Endolysins are by far the most studied group of peptidoglycan-degrading enzymes, with several studies showing that they can exhibit potent antibacterial activity under specific conditions. However, the lytic activity of most endolysins seems to be significantly reduced when tested against actively growing bacteria, something that may be related to fact that these enzymes are naturally designed to degrade the peptidoglycan from within dead cells. This may negatively impact the efficacy of the endolysin in treating some infections in vivo. Here, we present a critical view of the methods commonly used to evaluate in vitro and in vivo the antibacterial performance of PG-degrading enzymes, focusing on the major hurdles concerning in vitro-to-in vivo translation.
Topics: Animals; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Bacteriophages; Cell Wall; Endopeptidases; Humans; Mice; Peptidoglycan; Viral Proteins; Virion
PubMed: 29844287
DOI: 10.3390/v10060292 -
Current Biology : CB Jul 2021Dynamics of cell elongation and septation are key determinants of bacterial morphogenesis. These processes are intimately linked to peptidoglycan synthesis performed by...
Dynamics of cell elongation and septation are key determinants of bacterial morphogenesis. These processes are intimately linked to peptidoglycan synthesis performed by macromolecular complexes called the elongasome and the divisome. In rod-shaped bacteria, cell elongation and septation, which are dissociated in time and space, have been well described. By contrast, in ovoid-shaped bacteria, the dynamics and relationships between these processes remain poorly understood because they are concomitant and confined to a nanometer-scale annular region at midcell. Here, we set up a metabolic peptidoglycan labeling approach using click chemistry to image peptidoglycan synthesis by single-molecule localization microscopy in the ovoid bacterium Streptococcus pneumoniae. Our nanoscale-resolution data reveal spatiotemporal features of peptidoglycan assembly and fate along the cell cycle and provide geometrical parameters that we used to construct a morphogenesis model of the ovoid cell. These analyses show that septal and peripheral peptidoglycan syntheses first occur within a single annular region that later separates in two concentric regions and that elongation persists after septation is completed. In addition, our data reveal that freshly synthesized peptidoglycan is remodeled all along the cell cycle. Altogether, our work provides evidence that septal peptidoglycan is synthesized from the beginning of the cell cycle and is constantly remodeled through cleavage and insertion of material at its periphery. The ovoid-cell morphogenesis would thus rely on the relative dynamics between peptidoglycan synthesis and cleavage rather than on the existence of two distinct successive phases of peripheral and septal synthesis.
Topics: Bacteria; Bacterial Proteins; Cell Cycle; Cell Division; Cell Wall; Peptidoglycan; Streptococcus pneumoniae
PubMed: 33989523
DOI: 10.1016/j.cub.2021.04.041 -
Chemical Communications (Cambridge,... Nov 2020The interaction between host immunity and bacterial cells plays a pivotal role in a variety of human diseases. The bacterial cell wall component peptidoglycan (PG) is... (Review)
Review
The interaction between host immunity and bacterial cells plays a pivotal role in a variety of human diseases. The bacterial cell wall component peptidoglycan (PG) is known to stimulate an immune response, which makes PG a distinctive recognition element for unveiling these complicated molecular interactions. Pattern recognition receptor (PRR) proteins are among the critical components of this system that initially recognize molecular patterns associated with microorganisms such as bacteria and fungi. These molecular patterns are mostly embedded in the bacterial or fungal cell wall structure and can be released and presented to the immune system in various situations. Nonetheless, detailed knowledge of this recognition is limited due to the diversity among the PG polymer and its fragments; the subsequent responses by multiple hosts add more complexity. Here, we discuss how our understanding of the role and molecular mechanisms of the well-studied PRR, the NOD-like receptors (NLRs), in the human immune system has evolved in recent years. We highlight the instances of other classes of proteins with similar behavior in the recognition of PG that have been identified in other microorganisms such as yeasts. These proteins are particularly interesting because a network of cellular interactions exists between human host cells, bacteria and yeast as a part of the normal human flora. To support our understanding of these interactions, we provide insight into the chemist's toolbox of peptidoglycan probes that aid in the investigations of the behaviors of these proteins and other biological contexts relevant to the sensing and recognition of peptidoglycan. The importance of these interactions in human health for the development of biomarkers and biotherapy is highlighted.
Topics: Animals; Biosensing Techniques; Host-Pathogen Interactions; Humans; Immunity; Peptidoglycan
PubMed: 33057506
DOI: 10.1039/d0cc02605k -
Nature Communications Dec 2023The FtsEX complex regulates, directly or via a protein mediator depending on bacterial genera, peptidoglycan degradation for cell division. In mycobacteria and...
The FtsEX complex regulates, directly or via a protein mediator depending on bacterial genera, peptidoglycan degradation for cell division. In mycobacteria and Gram-positive bacteria, the FtsEX system directly activates peptidoglycan-hydrolases by a mechanism that remains unclear. Here we report our investigation of Mycobacterium tuberculosis FtsEX as a non-canonical regulator with high basal ATPase activity. The cryo-EM structures of the FtsEX system alone and in complex with RipC, as well as the ATP-activated state, unveil detailed information on the signal transduction mechanism, leading to the activation of RipC. Our findings indicate that RipC is recognized through a "Match and Fit" mechanism, resulting in an asymmetric rearrangement of the extracellular domains of FtsX and a unique inclined binding mode of RipC. This study provides insights into the molecular mechanisms of FtsEX and RipC regulation in the context of a critical human pathogen, guiding the design of drugs targeting peptidoglycan remodeling.
Topics: Humans; Cell Cycle Proteins; Mycobacterium tuberculosis; Hydrolases; Bacterial Proteins; Peptidoglycan; Cell Division
PubMed: 38044344
DOI: 10.1038/s41467-023-43770-6 -
PLoS Pathogens Dec 2015