Exchangers bacterial resistance

We have shown that the conformational behavior of natural aminoglycosides is characterized by a remarkable flexibility, with different conformations, even non-exo-anomeric ones, in fast exchange. This feature allows the adaptation of these ligands to the spatial and electronic requirements of the different receptors. The large diversity of structures adopted by aminoglycosides in the binding pocket of the different RNA receptors and the enzymes involved in bacterial resistance is consistent with this view. 

In some technological and medical applications protein adsorption and/or cell adhesion is advantageous, but in others it is detrimental. In bioreactors it is stimulated to obtain favourable production conditions. In contrast, biofilm formation may cause contamination problems in water purification systems, in food processing equipment and on kitchen tools. Similarly, bacterial adhesion on synthetic materials used for e.g. artificial organs and prostheses, catheters, blood bags, etc., may cause severe infections. Furthermore, biofilms on heat exchangers, filters, separation membranes, and also on ship hulls oppose heat and mass transfer and increase frictional resistance. These consequences clearly result in decreased production rates and increased costs. 

Figure 4.2. Proposed mechanism for tetracycline (TET) uptake and efflux across the bacterial cytoplasmic membrane. Mg, divalent magnesium cation TH2 and TH, protonaled and deproton-ated tetracycline, respectively TH Mg, magnesium-tetracycline chelate complex. Tet proteins confer resistance to tetracycline by mediating expulsion ofTH Mg from the cell in exchange for a...

FIGURE 5.3.14 The plasmid is a packet of supplemental DNA material found outside the bacterial chromosome. Plasmids often contain DNA molecules that serve specific purposes supplemental to chromosomal DNA. Genes for specific antibiotic resistance are found in plasmids, and genes conferring virulence are also found there. Exchange of plasmid DNA among bacteria is relatively easy. (From Amibile-Cuevas, C.E, Am. ScL, 91, 138, 2003. With permission.)... 

Experiments with penicillin show that resistant strains of staphylococci, even those that produce no penicillinase, take up no penicillin from solution, but susceptible strains of various species combine with from 200 to 750 molecules per cell. This amount is held tightly, cannot be washed away, and does not exchange with non-radioactive penicillin (Rowley et al., 1950 Maass and Johnson, 1949). The first molecules of penicillin are bound by inert material but, when this is saturated, the penicillin combines covalently with a receptor playing a key role in the biosynthesis of cell wall. Mammalian cells do not take up penicillin, but the bacterial cell binds it in less than 2 minutes. The penicillinbinding component is on the exterior, in the cytoplasmic membrane where the cell wall is synthesized. This component occurs in a phospholipid-containing fraction of staphylococci (Cooper, 1956). 

Although the natural penicillins, G (32) and V (33), are useful antibiotics in their own right, their development as major pharmaceutical products was limited until a convenient method for the exchange of their 6-amido side chain was discovered. The new side chains increase the antibiotic activity of the jS-lactam and improve their resistance to the bacterial jS-lactamases, which will hydrolyse the jS-lactam ring. These two effects create some very valuable commercial products whose annual sales exceed 10 . 

---