Thursday, January 23, 2014

BOLO Microbiology Daily Newsletter January 23, 2014 - Bacterial Cell Walls

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January 23, 2014 - Bacterial Cell Walls


The bacterial cell wall serves the same basic purpose as all cell walls, protection from hypotonic shock.  This protection is achieved by defining the shape and maximum size (volume) of the cell.  The cell membrane can swell to this set limit, but not beyond, thus preventing osmotic lysis.  Due to this hypotonic tolerance, bacterial cells can store higher concentrations of internal solutes than eukaryotic cells, which is advantageous to cells that lack internal compartmentalization.

A defining characteristic of Domain Bacteria is that bacterial cell walls are composed of peptidoglycan.  Glycans are large sugar chains, in this case made up of repeating N-acetylglutamic acid (NAG) and N-acetylmuramic acid (NAM).  Glycan chains are held together by peptide bridges.  Thus, we have peptidoglycan (peptide linked glycans).  In the image below, note how the oligopeptides (that make the peptide bridges) are attached to NAM.  Do you see how this resembles a chain link fence or chicken wire?

Chicken Wire and Chain Link Fence.
Peptidoglycan: http://en.wikipedia.org/wiki/File:Mureine.svg
The following image provides an overview of peptidoglycan synthesis in gram negative cells.  Note that this is a process started within the cytoplasm, but finished outside of the cell membrane.  It is because of this multistep synthesis that peptidoglycan can be targetted with antimicrobial drugs.
Peptidoglycan Synthesis:
Typas, A., Banzhaf, M., Gross, C.A., and Vollmer, W. (2012). From the regulation of peptidoglycan synthesis to bacterial growth and morphology. Nat Rev Micro 10, 123–136.


Since peptidoglycan is defining for bacteria, and not found in mammals, it makes an excellent target for drug therapies aimed at bacterial pathogens.  When you look at medical microbiology and drug development, you will note that a critical stage of developing safe drugs is to target something that is unique to the pathogen.  In this way, you can prevent host toxicity (beyond potential allergic effects).  Targeting a metabolic feature (like glycolysis) that is held in common would hurt the host as well as the pathogen.  [What drugs target peptidoglycan?]

The cell wall structure of bacteria takes on two major forms, referred to as gram + or gram -.  This designation comes from the result of Gram's Staining, a differential staining technique.  Gram + organisms have a large peptidoglycan wall, while gram - cells have a thin peptidoglycan and an outer membrane.  This difference is remarkable, and provides each group of bacteria with its own sets of advantages and limitations.

As a note:  the human immune system has the ability to register peptidoglycan as foreign.   Peptidoglycan is classified as a Pathogen Associated Molecular Pattern (PAMP).  It is picked up by the Toll-Like Receptor (TLR) 2 in human monocytes (innate immunity).  We'll bring this concept up later, but for now, look at the concept of a PAMP...specifically the idea of a molecular pattern. 


Today's Challenge:

Focus today on the gram + cell.  Provide a detailed description of the cell's structure and advantages that can be gained by having a large peptidoglycan cell wall.  Find two examples of gram + organisms, and give some information about these organisms.

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