Bacterial cell envelope

A biomolecular system of glycoproteins derived from bacterial cell envelopes that spontaneously aggregates to form crystalline arrays in the mesoscopic range is reviewed in Chapter 9. The structure and features of these S-layers that can be applied in biotechnology, membrane biomimetics, sensors, and vaccine development are discussed. 

Endotoxins are bacterial cell envelope constituents that, when present in pharmaceutical products, cause pyrogenic reactions sometimes resulting in lethality. The toxicity of endotoxins is directly related to their chemical composition. However, the viability of the organism is irrelevant since endotoxin derived from dead or live microbes is equally active. The classical endotoxin is lipopolysaccharide (LPS). However, peptidoglycan (PG) also displays endotoxin-like activities. LPS is found only in gram-negative bacterial outer membranes, while PG is present in the cell... 

Endotoxicity results from the interaction of a bacterial cell envelope component (e.g., LPS or PG with a cell surface receptor constituting part of the nonspecific immune system, (i.e., a toll-like receptor on white blood cells). This results in the production of cytokines [e.g., interleukin 1 (IL-1) or tumor necrosis factor (TNF)] as part of an intracellular enzyme cascade which can cause severe tissue injury. Bioassays or immunoassays can be used to detect such reactions respectively. As noted above the most widely used bioassay is the LAL assay. A lysate of amoebo-cytes of the horseshoe crab (Limulus) contains an enzymatic clotting cascade which is activated by extremely low levels of LPS (nanogram levels or lower). There are variants of this assay that can detect PG, but they are not as widely used. As noted above, other bioassays employ cultured cell lines that respond to LPS or PG, respectively. Unfortunately bioassays are highly amenable to false positives (from the presence of cross-reactive substances) or false negatives from inhibition (by contaminants present in the sample) [10]. A detailed discussion of these assays is beyond the scope of this chapter and has been reviewed elsewhere [1]. 

Neither the mechanisms of the host defence for eradication of challenging Salmonella bacteria, nor the relative importance of the host defence against the various Individual surface components of the bacterial cell envelope are well understood. Since, as was stated above, the O-antlgenic polysaccharide chains apparently play an important role in eliciting an effective host defence of either humoral or cellular nature, we have used the various saccharides described earlier for studies of this problem. 

Antibacterial antibiotics normally act by either making the plasma membrane of bacteria more permeable to essential ions and other small molecules by iono-phoric action or by inhibiting cell wall synthesis (see section 7.2.2). Those compounds that act on the plasma membrane also have the ability to penetrate the cell wall structure (Appendix 3). In both cases, the net result is a loss in the integrity of the bacterial cell envelope, which leads to irreversible cell damage and death. 

As the main surface component of the bacterial cell envelope LPS is thought to contribute to the restrictive Gram-negative membrane permeability, allowing bacterial growth in unfavourable environments such as those that may be encountered within or on plants. The exclusion of antimicrobial substances of plant origin probably contributes to the ability of pathogenic bacteria to parasitize plants. LPS-defective mutants show increased in vitro sensitivity to antibiotics and antimicrobial peptides and the numbers of viable bacteria often decline very rapidly upon introduction into plants. LPS may also promote bacterial adherence to plant surfaces (Newman et al., 2007). 

RNA-modulated cell-based assays can penetrate bacterial cell envelopes and possess antibacterial activity—desirable properties unusual for the majority of initial hits from biochemical assays. 

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