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.
Nozaki
Y
Y
Central Research Division, Takeda Chemical Industries, Ltd., Osaka, Japan.
Katayama
N
N
Harada
S
S
Ono
H
H
Okazaki
H
H
D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000494:pharmacology*; D001412:Bacillus subtilis / Q000187:drug effects; D001426:Bacterial Proteins; D002352:Carrier Proteins / Q000378:metabolism; D004926:Escherichia coli / Q000187:drug effects; D006602:Hexosyltransferases; D002267:Muramoylpentapeptide Carboxypeptidase / Q000378:metabolism; D046915:Penicillin-Binding Proteins; D010455:Peptides; D010456:Peptides, Cyclic / Q000378:metabolism / Q000494:pharmacology; D010458:Peptidyl Transferases; D013438:Sulfhydryl Compounds / Q000502:physiology
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D002352:Carrier Proteins; D046915:Penicillin-Binding Proteins; D010455:Peptides; D010456:Peptides, Cyclic; D013438:Sulfhydryl Compounds; C051231:lactivicin; D010458:Peptidyl Transferases; D006602:Hexosyltransferases; D002267:Muramoylpentapeptide Carboxypeptidase