Nozaki Y, Katayama N, Harada S, Ono H, Okazaki H
Central Research Division, Takeda Chemical Industries, Ltd., Osaka, Japan.
J Antibiot (Tokyo). 1989 Jan;42(1):84-93. doi: 10.7164/antibiotics.42.84.
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.
乳链菌肽对多种革兰氏阴性菌具有中等活性，对革兰氏阳性菌具有高活性。它表现出β-内酰胺类抗生素常见的多种生物活性，例如对β-内酰胺超敏突变体的活性高于其亲本、对β-内酰胺酶敏感、对β-内酰胺酶具有抑制活性以及能够诱导β-内酰胺酶活性。乳链菌肽在大肠杆菌中的主要致死靶点很可能是青霉素结合蛋白（PBP）1；乳链菌肽在其最低抑菌浓度（MIC）时能强烈裂解大肠杆菌细胞并诱导原生质体形成，且对PBP 1A和1B具有高亲和力。然而，在高于5倍MIC的浓度下，乳链菌肽主要表现出次要抗菌作用，这可能是由于抑制了参与基本膜功能的关键SH蛋白。相比之下，对于枯草芽孢杆菌，乳链菌肽在很宽的浓度范围内都表现出典型的β-内酰胺作用。它对PBP 1、2和4具有高亲和力，而这三种蛋白可能是β-内酰胺类抗生素在该生物体中的致死靶点。总之，乳链菌肽是第一种通过与PBPs结合而表现出β-内酰胺作用的非β-内酰胺类抗生素。
