Outer membranes: of bacteria

Approaches to the synthesis of glycosyl phosphate diesters as constituents of glycopolymers of the outer membrane of bacteria, yeasts and protozoa and the latest achievements in the field have been profoundly reviewed and will not be covered in this chapter.1,2... 

Porin, a protein from the outer membranes of bacteria such as E. coli and Rhodo-bacter capsulatus, represents a class of membrane proteins with a completely different type of structure. Structures of this type are built from P strands and contain essentially no a helices (Figure 12.20). 

In prokaryotes, the electron-driven proton pumps and ATP-synthesizing complex are located in the cytoplasmic membrane, the inner of two membranes. The outer membrane of bacteria, like that of mitochondria, is permeable to most small metabolites because of the presence of porins. 

P-Lactam antibiotics show their lethal effect by inhibiting the synthesis of bacterial peptidoglycan, thereby disrupting the cell morphology and eventually resulting in cell lysis and death. Because the antibacterial effect of P-lactam is affected by the permeability of the outer membrane of bacteria, it is important in the evaluation of drug efficiency... 

It is important to the performance of AMPs that they be efficient in killing bacteria and other pathogens but leave human cells unaffected. The basis for such selectivity is that membranes of bacteria and human cells have different compositions. For example, cholesterol is rich (up to about 45%) in human cell membranes, while it is replaced by ergosterol in fungi and absent in bacteria. There are also differences in phospholipid composition. For example, PC and SM are abundant in the outer layer of erythrocytes, which renders these essentially uncharged. In contrast, the outer membrane of bacteria is rich in anionic lipids, such as phosphatidylglycerol (PG), cardiolipin,... 

The outer membrane is permeable to most small metabolites coming from the cytosol since it contains porine, a 29 kDa transmembrane protein possessing a large pore. Porine is present in the mitochondria of all the eucaryotes as weU as in the outer membrane of bacteria. The intermembrane space contains adenylate kinase, which ensures interconversion of ATP, ADP and AMP. Oxidative phosphorylahon takes place in the inner mitochondrial membrane. The matrix, on the other hand, is the center of the reactions of the tricarboxylic acids cycle and of the oxidation of fatty acids. 

Some polymyxins are sold for second-line systemic therapy. Polymyxin B sulfate and colistimethate sodium can be used for intravenous, intramuscular, or intrathecal administration, especially for Pseudomonas aerupinosa mP QXiosis, but also for most other gram-negative organisms, such as those resistant to first-line antibiotics. Nephrotoxicity and various neurotoxicities are common in parenteral, but not in topical, use. Resistance to polymyxins develops slowly, involves mutation and, at least in some bacteria, adaptation, a poorly understood type of resistance that is rapidly lost on transfer to a medium free of polymyxin. Resistance can involve changes in the proteins, the lipopolysaccharides, and lipids of the outer membrane of the cell (52). Polymyxin and colistin show complete cross-resistance. 

As shown in Figure 9.24, the outer membrane of Gram-negative bacteria is coated with a highly complex lipopolysaccharide, which consists of a lipid group (anchored in the outer membrane) joined to a polysaccharide made up of long chains with many different and characteristic repeating structures... 

FIGURE 9,24 Lipopolysaccharide (LPS) coats the outer membrane of Gram-uegative > bacteria. The lipid portion of the LPS is embedded iu the outer membrane and is linked to a complex polysaccharide. 

Endotoxins are the lipopolysaccharides (LPS) of the outer membrane of Gram-negative bacteria. They trigger inflammatory reactions in the infected organism, activate complement and cause fever or even a septic shock. They act on toll-like receptors. 

The outer membrane of gram-negative bacteria is a permeability barrier that allows the passive diffusion of small hydrophilic antibiotics only through aqueous channels, the porins. Drugs larger than 800 Da are... 

A great deal of our current understanding of the structure and function of the outer membrane of Gram-negative bacteria has come from studies with Escherichia coli and Salmonella typhimurium. The permeability barrier function of the outer membrane can... 

Figure 7.7 Structure of a generalized LPS molecule. LPS constitutes the major structural component of the outer membrane of Gram-negative bacteria. Although LPSs of different Gram-negative organisms differ in their chemical structure, each consists of a complex polysaccharide component, linked to a lipid component. Refer to text for specific details...

TRANSPORT ACROSS THE OUTER MEMBRANE OF GRAM-NEGATIVE BACTERIA... 

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