Ristocetins, inhibitors of cell wall synthesis in Staphylococcus aureus.

Inhibition of bacterial cell wall synthesis is an important mechanism of action of antibacterial agents. Bacterial cell walls are chemically and morphologically distinct from any structures found in animal cells. Inhibition of synthesis of these structures results, therefore, in selective toxicity. The antibacterial action of penicillins (1, 2), n-cycloserine (3, 4), bacitracin (5), and novobiocin (6) is accompanied by inhibition of cell wall synthesis and, in the case of n-cycloserine, the identification of two enzymatic reactions sensitive to n-cycloserine and uniquely found in bacteria provides a relatively complete explanation of its antibacterial activity (7). Many of these laboratory studies have been carried out with Staphylococcus aureus. After the emergence of drug-resistant strains of X. aureus in infected humans, a search for new antistaphylococcal antibiotics resulted in the isolation of vancomycin (8) and ristocetin (9). Both of these have been widely used in the treatment of staphylococcal infections. Investigation of the mechanism of action of these two substances has resulted in the finding that both of them selectively inhibit bacterial cell wall synthesis at levels which are comparable with those required for antibacterial activity. While these experiments were in progress, two other laboratories reported similar experiments with vancomycin (10, 11) and, hence, only the results obtained with ristocetin will be reported here.