Mammalian cell wall

The cephalosporins have a broader spectrum of activity than penicillins and resistance is less common (see p 159). The low toxicity of the P-lactam antibiotics is due to the fact that the mammalian cell walls lack peptidoglycans and for this reason also lack the relevant enzymes. 

Stonehill, E. H., and Huppert, J., 1968, Ribonuclease activity associated with mammalian cell walls, Biochim. Biophys. Acta 155 353. 

The mechanism of antibacterial activity is through inhibition of gram-positive bacterial cell-wall synthesis thus, the penicillins are most effective against actively multiplying organisms. Because mammalian cells do not have a definitive cell-wall stmcture as do bacteria, the mammalian toxicity of the penicillins is low. Allergic phenomena in patients following sensitization may occur. 

In general, penicillins exert thek biological effect, as do the other -lactams, by inhibiting the synthesis of essential structural components of the bacterial cell wall. These components are absent in mammalian cells so that inhibition of the synthesis of the bacterial cell wall stmcture occurs with Htde or no effect on mammalian cell metaboHsm. Additionally, penicillins tend to be kreversible inhibitors of bacterial cell-wall synthesis and are generally bactericidal at concentrations close to thek bacteriostatic levels. Consequently penicillins have become widely used for the treatment of bacterial infections and are regarded as one of the safest and most efficacious classes of antibiotics. 

The biochemical basis of penicillin action continues to be an area of active investigation. Penicillins are highly specific inhibitors of enzyme(s) involved in the synthesis of the bacterial cell wall, a structure not present in mammalian cells. Three principal factors are thought to be important for effective antibacterial action by a penicillin ... 

The processes of electron transport and oxidative phosphorylation are membrane-associated. Bacteria are the simplest life form, and bacterial cells typically consist of a single cellular compartment surrounded by a plasma membrane and a more rigid cell wall. In such a system, the conversion of energy from NADH and [FADHg] to the energy of ATP via electron transport and oxidative phosphorylation is carried out at (and across) the plasma membrane. In eukaryotic cells, electron transport and oxidative phosphorylation are localized in mitochondria, which are also the sites of TCA cycle activity and (as we shall see in Chapter 24) fatty acid oxidation. Mammalian cells contain from 800 to 2500 mitochondria other types of cells may have as few as one or two or as many as half a million mitochondria. Human erythrocytes, whose purpose is simply to transport oxygen to tissues, contain no mitochondria at all. The typical mitochondrion is about 0.5 0.3 microns in diameter and from 0.5 micron to several microns long its overall shape is sensitive to metabolic conditions in the cell. 

The presence and biological importance of oligosaccharide structures, usually as components of glycolipids and glycoproteins, in bacterial capsular and cell-wall polysaccharides, in mammalian cell membranes, in cytoplasm, and in extracellular fluids, are now well documented. They are important constituents in... 

Submembranous microtubules are often present in parallel bundles beneath the plasma membrane in the cells of higher plants, particularly during cell wall formation (Hardham and Gimning, 1978). Circular submembranous bundles of microtubules are a feature of bird erythrocytes and mammalian blood platelets, where they maintain the discoid shape of these structures (Dustin, 1980). 

O. 05 pm to about 0.15 pm at a distance of about 300 pm away from the tip. Similar observations involving biopolymerisation reaction at the wall and an increase in cell wall thickness with cycle time have been reported for unicellular micro-organisms including mammalian and bacteria cells [63,67,73]. 

The perceived sensitivity of plant cells to the hydrodynamic stress associated with aeration and agitation conditions is typically attributed to the physical characteristics of the suspended cells, namely their size, the presence of a cell wall, the existence of a large vacuole, and their tendency to aggregate. Table 1 illustrates some of the differences between plant cells and other biological systems. Chalmers [19] attributed shear sensitivity in mammalian cultures at least in part to the fact that these cells occur naturally as part of a tissue, surrounded by other cells. The same is true for plant cells. The more robust microbial systems, on the other hand, exist in nature as single organisms or mycelial structures, very close to the forms they assume in submerged culture. 

In suspension, plant cells are significantly larger than most microbial cells and are typically of the order of 10-100 pm in size. They vary in shape from cylindrical to spherical. The plasma membrane is surrounded by a primary cell wall which defines the cell size and shape. The robustness of plant cells, relative to mammalian cells or to plant protoplasts [18], is usually attributed to the pre-... 

Dunlop [18] proposed a model for sub-lytic effects in plant cells, based on the same principles, but including four properties postulated to be of particular importance in these systems, namely calcium ion flux, osmo-regulation, cell-cell contact/aggregation and stress protein expression. Of these factors, osmo-regulation (and its inter-relationship with the cell wall) and aggregation patterns, in particular, distinguish plant cells from mammalian cell systems. 

Bacterial cell wall j3-Lactams Glyoopeptides Cycloserine Isoniazid Ethambutol Inhibit peptidoglycan synthesis Inhibit peptidoglycan synthesis Inhibits peptidoglycan synthesis Inhibits mycolic acid synthesis Inhibits arabinogalactan synthesis None in mammalian cells None in mammalian cells None in mammalian cells None in mammalian cells None in mammalian cells... 

The DNA or cDNA library is then introduced into a preparation of bacterial host cells. Usually, the first host selected is a laboratory strain of E. coli which has been grown and pretreated with inorganic salts to make uptake of DNA easier. The ability to take up foreign DNA is called competence, cells which have been specially prepared for the purpose are called competent cells. Other methods to transfer DNA into cells include electroporation (application of an external electric field to permeabUize the cell wall), transfection (where a recombinant bacterial virus is used to transfer the DNA to the target cell) or ballistic methods (by using DNA-coated particle projectiles). The last method has been used to introduce foreign DNA into plant cells and mammalian cells. 

At the outset, recognize that there are many types of biological membranes some surround complex viruses others occupy a space inside the bacterial cell wall and still others isolate mammalian cells from their enviromnent. 

The pathway from simple molecules to the peptidoglycan of the bacterial cell wall is lengthy and complex. Many of the details are well known but need not concern us here. Suffice it to say that long carbohydrate chains are synthesized, subsequently decorated with shorter amino acid chains, and these are finally cross-linked to provide a strong strnctnre. It is this final cross-linking step that is inhibited by the p-lactam antibiotics. The consequence is that cell wall biosynthesis cannot be completed and cell death ensnes. Again, the mammalian host carries out no similar reactions so that similar consequences do not ensne for the host orgaiusm. 

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