II. THE PROKARYOTIC CELL: BACTERIA
B. PROKARYOTIC CELL STRUCTURE
2c. The Acid-Fast Cell Wall
The overall purpose of this Learning Object is:
1) to learn the chemical makeup and functions associated with the cell wall of acid-fast bacteria;
2) to introduce the relationship between components of the acid-fast cell wall and the initiation of body defenses; and
3) to introduce the relationship between components of the acid-fast cell wall and bacterial pathogenicity.
LEARNING OBJECTIVES FOR THIS SECTION
In this section on Prokaryotic Cell
Structure we are looking at the various organelles or structures that make up
a bacterium. As mentioned in the introduction to this section, a typical bacterium
usually consists of:
There are three primary types of bacterial cell wall: gram-positive, gram-negative, and acid-fast. We will now look at the acid-fast cell wall.
The Acid-Fast Cell Wall (def)
Acid-fast bacteria stain poorly with the Gram stain procedue, appearing weakly gram-positive or gram-variable. They are usually characterized using the acid-fast staining procedure. As mentioned in the previous section on peptidoglycan, bacteria with an acid-fast cell wall resist decolorization with an acid-alcohol mixture during the acid-fast staining procedure , retain the initial dye carbol fuchsin and appear red. Common acid-fast bacteria of medical importance include Mycobacterium tuberculosis, Mycobacterium leprae,Mycobacterium avium-intracellulare complex, and Nocardia species.
- Scanning electron micrograph of Mycobacterium tuberculosis; courtesy of CDC
- Photomicrograph showing a positive acid-fast stain of Mycobacterium tuberculosis in sputum.
A. Structure and Composition of the Acid-Fast Cell Wall
Acid-fast bacteria are gram-positive, but in addition to peptidoglycan, the outer membrane or envelope of the acid-fast cell wall of contains large amounts of glycolipids, especially mycolic acids that in the genus Mycobacterium, make up approximately 60% of the acid-fast cell wall.
1. The acid-fast cell wall of Mycobacterium has a thin, inner layer of peptidoglycan (see Fig. 1).
2. The peptidoglycan layer is, in turn, linked to arabinogalactan (D-arabinose and D-galactose) as shown in Fig. 1.
3. The arabinogalactan is then linked to an outer membrane containing high-molecular weight mycolic acids. The arabinogalactan/mycolic acid layer is overlaid with a layer of polypeptides and mycolic acids consisting of free lipids, glycolipids, and peptidoglycolipids. Other glycolipids include lipoarabinomannan and phosphatidyinositol mannosides (PIM). Like the outer membrane of the gram-negative cell wall, porins are required to transport small hydrophilic molecules through the outer membrane of the acid-fast cell wall (see Fig. 1).
4. The outer surface of the acid-fast cell wall is studded with surface proteins that differ with the strain and species of the bacterium.
5. The periplasm is the gelatinous material between the peptidoglycan and the cytoplasmic membrane.
B. Functions of the Acid-Fast Cell Wall Components
1. The peptidoglycan prevents osmotic lysis (def).
2. The arabinogalactan layer is linked to both the peptidoglycan and to the mycolic acid outer membrane and probably provides additional strength to the cell wall.
3. The mycolic acids and other glycolipids also impede the entry of chemicals causing the organisms to grow slowly and be more resistant to chemical agents and lysosomal components of phagocytes than most bacteria (see Fig. 1). There are far fewer porins in the acid-fast cell wall compared to the gram-negative cell wall and the pores are much longer. This is thought to contribute significantly to the lower permeability of acid-fast bacteria.
4. The surface proteins in the acid-fast cell wall, depending on the strain and species, carry out a variety of activities, including:
- Functioning as enzymes.
- Serving as adhesins (def). Adhesins enable the bacterium to adhere intimately to host cells and other surfaces in order to colonize and resist flushing.
5. The periplasm contains enzymes for nutrient breakdown.
C. Significance of Acid-Fast Cell Wall Components to the Initiation of Body Defenses
1. In order to protect against infection, one of the things the body must initially do is detect the presence of microorganisms. The body does this by recognizing molecules unique to microorganisms that are not associated with human cells. These unique molecules are called pathogen-associated molecular patterns or PAMPs (def). Pathogenic Mycobacterium species such as Mycobacterium tuberculosis (inf) and Mycobacterium leprae (inf) release mycolic acid, arabinogalactan, and peptidoglycan fragments from their acid-fast cell wall. (Because all microbes, not just pathogenic microbes, possess PAMPs, pathogen-associated molecular patterns are sometimes referred to as microbe-associated molecular patterns or MAMPs.)
These PAMPS bind to pattern-recognition receptors or PRRs (def) on a variety of defense cells of the body causing them to synthesize and secrete a variety of proteins called cytokines. These cytokines can, in turn promote innate immune defenses such as inflammation (def), phagocytosis, activation of the complement pathways (def), and activation of the coagulation pathway (def).
Inflammation (def) is the first response to infection and injury and is critical to body defense. Basically, the inflammatory response is an attempt by the body to restore and maintain homeostasis (def) after injury. Most of the body defense elements are located in the blood, and inflammation is the means by which body defense cells and body defense chemicals leave the blood and enter the tissue around an injured or infected site.
Body defense cells called macrophages (def), and dendritic cells (def) have pattern recognition receptors such as toll-like receptors on their surface that are specific for the peptidoglycan fragments and mycolic acids in the acid-fast cell wall and/or to NODs in their cytoplasm that are specific for peptidoglycan fragments. The binding of these cell wall components to their corresponding pattern recognition receptors triggers the macrophages to release various defense regulatory chemicals called cytokines (def), including IL-1 and TNF-alpha. The cytokines then bind to cytokine receptors on target cells and initiate inflammation and activate both the complement pathways (def) and the coagulation pathway.
D. Significance of Acid-Fast Cell Wall Components to Bacterial Pathogenicity
Most of the damage in the lungs during tuberculosis is thought to be due to the inflammatory effects from excessive TNF-alpha production, along with the release of toxic lysosomal components of the macrophages trying to kill the Mycobacterium tuberculosis.
Highlighted Bacterium: Mycobacterium tuberculosis
Click on this link, read the description of Mycobacterium tuberculosis, and be able to match the bacterium with its description on an exam.
E. Antimicrobial Agents that Inhibit Acid-Fast Cell Wall Synthesis to Control Mycobacterium Species
INH (isoniazid) blocks the incorporation of mycolic acid into acid-fast cell walls while ethambutol interferes with the incorporation of arabinoglactan (see Fig. 1) . Both inhibit synthesis of the acid-fast cell wall. Pyrazinamide inhibits fatty acid synthesis in Mycobacterium tuberculosis.
E-Medicine article on infections associated with organisms mentioned in this Learning Object. Registration to access this website is free.
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Updated: April, 2011
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