Suppression of Peptidoglycan Remodeling
By [Frank Zhao]
Peptidoglycan is a polymer made of sugars and amino acids that forms a layer outside the plasma membrane of bacterial cells. Peptidoglycans are cross-linked by peptides, serving as the cell wall that protects bacteria from the environment. Peptidoglycan limits the volume of the cell and thus it generates turgor pressure as the water rushes into the cell. Gram-positive bacteria obtain a thicker peptidoglycan layer than Gram-negative bacteria but this layer is crucial to the survival of both types of bacteria.
Many antibiotics target this component to kill the bacteria. For example, penicillin binds to penicillin-binding proteins and inhibits the synthesis of peptidoglycan, weakening the cell wall of bacteria. It has been discovered that a new mechanism could be used by antibiotics on peptidoglycan— blocking the action of autolysins, a peptidoglycan hydrolase that is essential for remodeling the bacterial cell wall during growth. Studying how this new mechanism works could give us insight into developing new antibiotics against resistant strains.
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Structure and Function
The peptidoglycan layer is located in the bacterial cell wall, consisting of chains of two alternating amino sugars, N-acetylglucosamine (an amide derivative of the monosaccharide glucose) and N-acetylmuramic acid (a combination of N-acetylglucosamine and phosphoenolpyruvate). The alternating amino sugars are linked by Teichoic acids, which are chains of phosphodiester-linked glycerol or ribitol. Parallel chains of amino sugars can also be connected by cross-bridges made of extensions of peptides to form tetrapeptides, with m-Diaminopimelic acid binding D-Alanine.<ref> Bruslind, Linda. n.d. “Bacteria: Cell Walls.” in General Microbiology. Oregon State University.Cite error: The opening
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Peptidoglycan sacculi cross-linked by peptides form a closed, sac-shaped structure that surrounds the cytoplasmic membrane. Peptidoglycan sacculi have been purified from Escherichia coli by incubation with boiling 4% sodium dodecyl sulfate.<ref> Vollmer, Waldemar, Didier Blanot, and Miguel A. de Pedro. 2008. “Peptidoglycan Structure and Architecture.” FEMS Microbiology Reviews 32(2):149–67. doi: 10.1111/j.1574-6976.2007.00094.x.Cite error: The opening
<ref> tag is malformed or has a bad name While a bacterial cell contains a significant number of different kinds of molecules, there is only one peptidoglycan molecule in each bacterial cell, which contributes to 0.8% of the mass of the whole cell.
Include some current research, with at least one figure showing data.
Inhibitive Antibiotics Targeting Peptidoglycan
Corbomycin and Complestatin
- Slonczewski, J., and Foster J. W.. Microbiology: An Evolving Science. New York
- Anon. n.d. “Bacteria.” Basic Biology. Retrieved April 8, 2021
-  Culp, Elizabeth J., Nicholas Waglechner, Wenliang Wang, Aline A. Fiebig-Comyn, Yen-Pang Hsu, Kalinka Koteva, David Sychantha, Brian K. Coombes, Michael S. Van Nieuwenhze, Yves V. Brun, and Gerard D. Wright. 2020. “Evolution-Guided Discovery of Antibiotics That Inhibit Peptidoglycan Remodelling.” Nature 578(7796):582–87. doi: 10.1038/s41586-020-1990-9.
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