Bactericidal 447 Disaccharides

When rabbits were immunized with the glycoconjugates suspended in Freund s complete adjuvant antibodies with specificity for the haptenic disaccharides were produced, as estimated in passive hemagglutination and complement-mediated bactericidal tests, and enzyme-linked immunosorbent assay (ELISA) (12-15). 

In terms of the bactericidal effect, note that a 16-membered-ring macrolide, which bears at least one disaccharide-monoglycoside residue related to a stable binding (probably deposition binding) to ribosome, causes polyribosome degradation [93,94]. 

In addition to demonstrating a unique spectrum of antibacterial activity, the disaccharide analogs also demonstrated antibacterial characteristics that differ from moenomycin itself. Analysis of analogs 30, 31, and 32 showed that these compounds were substantially more bactericidal than moenomycin. They demonstrated 4 to 6 log units of killing when Gram-positive bacteria were treated with 4 to 8 times their MIC as compared to 1 log unit of killing when treated with 100 times the MIC of moenomycin (Figure 8.11). 

Experimental evidence also supported the hypothesis that the disaccharide analogs inhibit bacterial growth by inhibiting cell wall biosynthesis. They demonstrated bactericidal activity only in actively growing cells, and cells pretreated with protein synthesis inhibitors were resistant to the effects of the disaccharide analogs. In addition, they inhibited incorporation of lysine into cell wall material in intact Ent. faecalis. ... 

FIGURE 8.11 Bactericidal effect of moenomycin and disaccharide analog 31 on Gram-positive bacteria (S. aureus and S. epidermidis). Moenomycin was added to 100 times MIC and disaccharide analog 31 added to 8 times MIC. C.f.u. s were determined by plating serial dilutions at various times following drug addition. 

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