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Related Concept Videos

Lysosomes01:31

Lysosomes

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Lysosomes are membrane-enclosed spherical sacs derived from the Golgi apparatus. The most important function of the lysosome is degrading macromolecules and biological polymers that are released during membrane trafficking events such as the secretory, endocytic, autophagic, and phagocytic pathways. The degradation is carried out by several hydrolytic enzymes active in an acidic environment of the lysosomal lumen. These acid hydrolases are involved in cellular processes such as cell signaling,...
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Lysosomes are the site for the degradation of macromolecules and biological polymers released during membrane trafficking events such as secretory, endocytic, autophagic, and phagocytic pathways. The membrane-enclosed area of the lysosome, called the lumen, contains hydrolytic enzymes active in an acidic environment. These acid hydrolases are functional at a pH between 4.5 and 5 and are involved in cellular processes such as cell signaling, energy metabolism, restoration of the plasma membrane,...
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Defense Against Bacterial Pathogens01:31

Defense Against Bacterial Pathogens

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The human immune system is a complex network of cells, tissues, and organs that work together to defend the body against bacterial infections. It consists of various immune cells, each playing a specific role in the defense mechanism.
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Eukaryotic cells use different mechanisms to eliminate toxic waste obsolete and worn-out substances. Lysosomes play a pivotal role in this, and hence, these substances are carried to the lysosome from other parts of the cell and extracellular space through different pathways. The most elaborately studied pathways to the lysosome are the endocytic pathways.
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Structure of Porins01:21

Structure of Porins

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Mitochondria, chloroplasts, and gram-negative bacteria have transmembrane, beta-barrel proteins called porins to mediate the free diffusion of ions and metabolites across the membrane. Mitochondrial porin precursors contain conserved amino acid sequences called beta signals at their C-terminal. Beta signals have a  motif of PoXGXXHyXHy (Po-Polar, X-Any amino acid, G-Glycine, Hy-LargeHydrophobic), which are crucial for precursor recognition to initiate precursor assembly. Beta-barrel...
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Surface Membrane Barriers01:18

Surface Membrane Barriers

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The skin and mucous membranes serve as the primary line of defense against pathogens by providing both physical and chemical protection. These barriers are essential in preventing the entry and establishment of microbes, thereby maintaining the integrity of the host.
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Separation of the Cell Envelope for Gram-negative Bacteria into Inner and Outer Membrane Fractions with Technical Adjustments for Acinetobacter baumannii
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Gram-negative endolysins: overcoming the outer membrane obstacle.

Hazel M Sisson1, Simon A Jackson2, Robert D Fagerlund2

  • 1Department of Microbiology and Immunology, University of Otago, PO Box 56, Dunedin 9054, New Zealand; Genetics Otago, University of Otago, PO Box 56, Dunedin 9054, New Zealand; Bioprotection Aotearoa, University of Otago, PO Box 56, Dunedin 9054, New Zealand.

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New strategies are needed to combat Gram-negative bacterial infections due to antimicrobial resistance. Phage-derived endolysins show promise, but their access to the bacterial peptidoglycan is blocked by the outer membrane (OM).

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Area of Science:

  • Microbiology
  • Biotechnology
  • Antimicrobial Research

Background:

  • Rising antimicrobial resistance in Gram-negative pathogens necessitates novel therapeutic strategies.
  • Endolysins, enzymes from bacteriophages, degrade peptidoglycan and are potential antimicrobial agents.
  • The outer membrane (OM) of Gram-negative bacteria presents a significant barrier to externally applied endolysins.

Purpose of the Study:

  • To review recent advancements in identifying endolysins capable of penetrating the Gram-negative OM.
  • To explore chemical and engineering strategies for enhancing endolysin efficacy against Gram-negative pathogens.

Main Methods:

  • Literature review of natural endolysin discovery and characterization.
  • Analysis of chemical modifications and engineering approaches to improve endolysin activity.
  • Focus on overcoming the OM barrier in Gram-negative bacteria.

Main Results:

  • Identification of natural endolysins with inherent OM-breaching capabilities.
  • Development of strategies to enhance endolysin penetration and antimicrobial efficacy.
  • Demonstration of increased effectiveness of modified endolysins against Gram-negative pathogens.

Conclusions:

  • Endolysins represent a promising alternative to conventional antibiotics for Gram-negative infections.
  • Overcoming the OM barrier is crucial for the therapeutic application of endolysins.
  • Continued research into endolysin discovery and engineering will advance their clinical potential.