Lactivicin, a naturally occurring non-beta-lactam antibiotic having beta-lactam-like action: biological activities and mode of action

Lactivicin is moderately active against a wide range of Gram-negative bacteria and highly active against Gram-positive bacteria. It shows various biological activities commonly observed with Beta-lactam Antibiotics, such as higher activity against beta-lactam hypersensitive mutants than against their parents, sensitivity to beta-lactamases, inhibitory activity against beta-lactamases and ability to induce Beta-lactamase activity. The primary lethal target of lactivicin in Escherichia coli is highly likely to be penicillin-binding protein (PBP) 1; lactivicin strongly lysed E. coli cells with induction of spheroplasts at its MIC, and showed high affinity for PBPs 1A and 1B. At concentrations above x 5 MIC, however, lactivicin dominantly exhibited secondary Antibacterial action possibly owing to inhibition of crucial SH proteins engaged in the fundamental membrane functions. In contrast, against Bacillus subtilis, lactivicin showed the typical beta-lactam action under a wide range of concentrations. It showed high affinity for PBPs 1, 2 and 4, the possible lethal targets of Beta-lactam Antibiotics in this organism. In conclusion, lactivicin is the first non-beta-lactam Antibiotic showing beta-lactam action through binding to PBPs.