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Category: Bacterial Pathogenesis
Target Tissues for Bacterial Adhesion, Page 1 of 2
< Previous page | Next page > /docserver/preview/fulltext/10.1128/9781555817800/9781555812638_Chap03-1.gif /docserver/preview/fulltext/10.1128/9781555817800/9781555812638_Chap03-2.gifAbstract:
A thorough understanding of cell and tissue biology is critical to the identification of the mechanisms of bacterial adhesion that operate within the host, especially in order to develop methods to selectively prevent pathogen adhesion. This chapter discusses some basic elements of cell biology that are relevant to bacterial adhesion. The distinction between membrane constituents as integral, peripheral, or belonging to the cell coat or extracellular matrix is based to some extent on the method required to dissociate the constituent in question from the cell membrane. The extracellular domains of integrins are located preferentially, but not exclusively, on basolateral surfaces of epithelial cells, where they bind to basal lamina components and other extracellular matrix macromolecules, while the cytoplasmic domains interact with cytoskeletal components and other cytoplasmic signaling partners. The peripheral membrane proteins and glycoproteins are anchored to the surface of the membrane by weak ionic interactions or by hydrogen bonding with integral constituents of the cell membranes, e.g., glycoproteins, glycolipids, or polar head groups of phospholipids. Some key examples of peripheral and extracellular components important for bacterial adhesion are discussed in the chapter. Changes are also bound to occur in cells exposed to the actions of drugs, some of which may affect the biosynthesis and expression of cell membrane constituents. Such changes have been best documented in carbohydrate residues of glycoproteins and glycolipids, largely due to the availability of specific lectin and gycosidase probes.
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Schematic illustration of stratified (A) and simple (B) epithelia. Stratified epithelia, such as stratified squamous epithelium of the pharyngeal mucosa (A), have up to 20 or more layers of cells. The basal layer of cuboidal cells lies on a basal lamina composed primarily of type IV collagen, laminin, heparan sulfate proteoglycans, fibronectin, and other extracellular matrix components. The cells are joined by a variety of junctional complexes composed, for instance, of tight junctions, desmosomes, and gap junctions (see also Fig. 3.2 ). The cells differentiate and change shape as they come closer to the luminal surface. The apical (luminal) surfaces of the squamous cells are covered with a mucus blanket, except for the skin, where the superficial cells are protected by becoming keratinized. In the buccal and pharyngeal epithelium, the mucus coat is not very thick. Nevertheless, to become attached, bacteria must be able to bind to mucus components, and before they are able to attach directly to epithelial cells, they must be able to penetrate or destroy the mucus blanket. Simple epithelia, such as the simple columnar epithelium lining most of the lower gastrointestinal tract (B), have only a single layer of cells. The majority of the cells are enterocytes, but mucus-producing goblet cells are interspersed with them. Specialized areas of the GALT called Peyer's patches are also found along the length of the intestine (see Fig. 3.3 ). The apical surface of each cell borders the lumen, and the basal layer rests on a basal lamina. The mucus blanket covering most of the intestinal surfaces is very thick, ranging up to 500 μm, several times thicker than the height of the cells. As in panel A, to gain attachment, bacteria must have adhesins for the mucus components. To enter the mucus blanket, bacteria frequently must be able to cycle between adhesive and nonadhesive phases. Once within this blanket, the bacteria can withstand being swept away by the much more rapid flows of fluid within the intestinal lumen (indicated by different- sized arrows).
Schematic illustration of stratified (A) and simple (B) epithelia. Stratified epithelia, such as stratified squamous epithelium of the pharyngeal mucosa (A), have up to 20 or more layers of cells. The basal layer of cuboidal cells lies on a basal lamina composed primarily of type IV collagen, laminin, heparan sulfate proteoglycans, fibronectin, and other extracellular matrix components. The cells are joined by a variety of junctional complexes composed, for instance, of tight junctions, desmosomes, and gap junctions (see also Fig. 3.2 ). The cells differentiate and change shape as they come closer to the luminal surface. The apical (luminal) surfaces of the squamous cells are covered with a mucus blanket, except for the skin, where the superficial cells are protected by becoming keratinized. In the buccal and pharyngeal epithelium, the mucus coat is not very thick. Nevertheless, to become attached, bacteria must be able to bind to mucus components, and before they are able to attach directly to epithelial cells, they must be able to penetrate or destroy the mucus blanket. Simple epithelia, such as the simple columnar epithelium lining most of the lower gastrointestinal tract (B), have only a single layer of cells. The majority of the cells are enterocytes, but mucus-producing goblet cells are interspersed with them. Specialized areas of the GALT called Peyer's patches are also found along the length of the intestine (see Fig. 3.3 ). The apical surface of each cell borders the lumen, and the basal layer rests on a basal lamina. The mucus blanket covering most of the intestinal surfaces is very thick, ranging up to 500 μm, several times thicker than the height of the cells. As in panel A, to gain attachment, bacteria must have adhesins for the mucus components. To enter the mucus blanket, bacteria frequently must be able to cycle between adhesive and nonadhesive phases. Once within this blanket, the bacteria can withstand being swept away by the much more rapid flows of fluid within the intestinal lumen (indicated by different- sized arrows).
Schematic illustration of the basic components of intestinal epithelial cells (enterocytes). The apical surface of enterocytes have microvilli (i.e., the brush border). The microvilli are filled with contractile elements of the cytoskeleton and coated with a glycocalyx (see the text). Covering the microvilli and glycocalyx is a mucus blanket that can be up to 500 μm thick (see the text for a description of its composition). The cells contain typical organelles, such as the nucleus, endoplasmic reticulum, and Golgi apparatus. They are joined by junctional complexes such as tight junctions, desmosomes, and gap junctions. The basal surface of the cells rests on a basal lamina composed of type IV collagen, laminin, heparan sulfate proteoglycans, fibronectin, and other extracellular matrix components. Fibrillar collagen, as well as other elements not illustrated (blood vessels and a variety of cell types, such as macrophages and mast cells), are found beneath the basal lamina. The cells are joined to the basal lamina by integrins. Cadherins, integrins, and connexins are localized preferentially but not exclusively to the basolateral membranes.
Schematic illustration of the basic components of intestinal epithelial cells (enterocytes). The apical surface of enterocytes have microvilli (i.e., the brush border). The microvilli are filled with contractile elements of the cytoskeleton and coated with a glycocalyx (see the text). Covering the microvilli and glycocalyx is a mucus blanket that can be up to 500 μm thick (see the text for a description of its composition). The cells contain typical organelles, such as the nucleus, endoplasmic reticulum, and Golgi apparatus. They are joined by junctional complexes such as tight junctions, desmosomes, and gap junctions. The basal surface of the cells rests on a basal lamina composed of type IV collagen, laminin, heparan sulfate proteoglycans, fibronectin, and other extracellular matrix components. Fibrillar collagen, as well as other elements not illustrated (blood vessels and a variety of cell types, such as macrophages and mast cells), are found beneath the basal lamina. The cells are joined to the basal lamina by integrins. Cadherins, integrins, and connexins are localized preferentially but not exclusively to the basolateral membranes.
Schematic illustration of a segment of the follicle-associated epithelium of a Peyer's patch. M cells have much shorter surface projections than do the surrounding enterocytes, and the mucus blanket is essentially absent. Absence of the mucus blanket allows microbes relatively free access to the apical membrane of M cells. Leukocytes are present within a compartment between the M-cell basolateral membrane and the basal lamina. The basal lamina underlying M cells is incomplete.
Schematic illustration of a segment of the follicle-associated epithelium of a Peyer's patch. M cells have much shorter surface projections than do the surrounding enterocytes, and the mucus blanket is essentially absent. Absence of the mucus blanket allows microbes relatively free access to the apical membrane of M cells. Leukocytes are present within a compartment between the M-cell basolateral membrane and the basal lamina. The basal lamina underlying M cells is incomplete.
Schematic composite illustration of the various components of animal cell membranes. The components illustrated vary depending on the cell type and on whether the membrane under discussion is the apical or basolateral membrane. Other than the lipid bilayer, the integral membrane components consist of integral membrane glycoproteins (e.g., integrins) and proteoglycans (e.g., syndecan), GPI-linked glycoproteins (e.g., CD14) and proteoglycans (e.g., glypican), and glycolipids (e.g., globoseries glycolipids). Peripheral components consist of glycoproteins such as fibronectin and laminin. The cell coat consists of the much more heavily glycosylated mucins and other components of the mucus blanket (see the text). Fibronectins and laminins would be present in greater amounts on basolateral surfaces, while mucins would be present in greater amounts on apical surfaces. The integral membrane proteins are linked to the actin cytoskeleton via linking elements such as talin, α-actinin, and vinculin.
Schematic composite illustration of the various components of animal cell membranes. The components illustrated vary depending on the cell type and on whether the membrane under discussion is the apical or basolateral membrane. Other than the lipid bilayer, the integral membrane components consist of integral membrane glycoproteins (e.g., integrins) and proteoglycans (e.g., syndecan), GPI-linked glycoproteins (e.g., CD14) and proteoglycans (e.g., glypican), and glycolipids (e.g., globoseries glycolipids). Peripheral components consist of glycoproteins such as fibronectin and laminin. The cell coat consists of the much more heavily glycosylated mucins and other components of the mucus blanket (see the text). Fibronectins and laminins would be present in greater amounts on basolateral surfaces, while mucins would be present in greater amounts on apical surfaces. The integral membrane proteins are linked to the actin cytoskeleton via linking elements such as talin, α-actinin, and vinculin.
(A) Uniform binding of lipoteichoic acid (LTA) to polymorphonuclear leukocytes in the absence of a cross-linking agent. (B and C) Capping that occurs 5 to 30 min after exposure to anti-lipoteichoic acid antibodies. (Reprinted from reference 13 with permission from the publisher.)
(A) Uniform binding of lipoteichoic acid (LTA) to polymorphonuclear leukocytes in the absence of a cross-linking agent. (B and C) Capping that occurs 5 to 30 min after exposure to anti-lipoteichoic acid antibodies. (Reprinted from reference 13 with permission from the publisher.)
Schematic illustration of the fibronectin monomer, its type I (GEOMETIC SHAPE), II ( GEOMETIC SHAPE) and III (GEOMETIC SHAPE) domains, and an indication of some of their binding activities. ED-A and ED-B indicate the “extra” domains that are spliced into or out of some fibronectin variants. (B) Disulfide-linked dimer of fibronectin.
Schematic illustration of the fibronectin monomer, its type I (GEOMETIC SHAPE), II ( GEOMETIC SHAPE) and III (GEOMETIC SHAPE) domains, and an indication of some of their binding activities. ED-A and ED-B indicate the “extra” domains that are spliced into or out of some fibronectin variants. (B) Disulfide-linked dimer of fibronectin.
Schematic illustration of cartilage proteoglycans linked to hyaluronan. Chondroitin sulfate and dermatan sulfate glycosaminoglycan chains are covalently linked to serine residues of core proteins. These are, in turn, linked to hyaluronan (hyaluronic acid) by link proteins to form the cartilage proteoglycan, also called aggrecan.
Schematic illustration of cartilage proteoglycans linked to hyaluronan. Chondroitin sulfate and dermatan sulfate glycosaminoglycan chains are covalently linked to serine residues of core proteins. These are, in turn, linked to hyaluronan (hyaluronic acid) by link proteins to form the cartilage proteoglycan, also called aggrecan.
Schematic illustration of a mucin monomer. (A) Large numbers of O-linked and a few N-linked oligosaccharide chains are bound to the apomucin protein. (B) Cross section showing that the oligosaccharide chains take on a radial arrangement.
Schematic illustration of a mucin monomer. (A) Large numbers of O-linked and a few N-linked oligosaccharide chains are bound to the apomucin protein. (B) Cross section showing that the oligosaccharide chains take on a radial arrangement.
Examples of bacteria taken up by M cells a
Examples of bacteria taken up by M cells a
Some important integral membrane components of epithelial cells that act as receptors for bacterial adhesins
Some important integral membrane components of epithelial cells that act as receptors for bacterial adhesins
Examples of bacteria that bind to heparan sulfate proteoglycan receptors
Examples of bacteria that bind to heparan sulfate proteoglycan receptors