Lleó M M, Canepari P, Cornaglia G, Fontana R, Satta G
Istituto di Microbiologia dell'Università di Verona, Italy.
Antimicrob Agents Chemother. 1987 Oct;31(10):1618-26. doi: 10.1128/AAC.31.10.1618.
The MICs and MBCs of benzylpenicillin, ampicillin, cefotaxime, and methicillin were evaluated against a Streptococcus (Enterococcus) faecium wild-type strain and against three mutants hyperproducing PBP 5 in cells incubated at both optimal and suboptimal temperatures. In the wild-type strain grown at optimal temperature, the MBCs of all beta-lactams were significantly greater than the MICs (bacteriostatic effect). As opposed to this, in the same cells grown at suboptimal temperature and in the mutants hyperproducing PBP 5 at all temperatures, the MICs of all antibiotics coincided with the MBCs (bactericidal effect). Under all conditions in which the MIC and MBC were the same, with all antibiotics, growth inhibition occurred only at the minimal concentration saturating all penicillin-binding proteins (PBPs) (or at higher concentrations). On the contrary, under conditions in which the MIC was lower than the MBC, only some of the PBPs were saturated (or bound) at both the MIC and the MBC, PBP 5 in no case being either saturated or bound. Under all conditions in which saturation of all PBPs was needed for growth inhibition, cells died at all antibiotic MBCs with kinetics which were much faster than those with which they died at the MBCs under conditions in which not all PBPs were saturated (or bound). In addition, under the former conditions, antibiotic concentrations above the MBCs did not significantly accelerate cell death kinetics, while under the latter conditions there was an acceleration in kinetics with increasing antibiotic concentrations up to full saturation of PBPs. It is suggested that the killing that occurs when all PBPs are saturated is a direct consequence of inactivation of PBP functions, while killing occurring when only some of them are saturated or bound is also (or mainly) an indirect consequence of inability of cells to grow and that, in S. faecium, the targets for growth inhibition and cell killing reside in different PBPs: for the latter effect, inactivation of one (or more) of the high-molecular-weight PBPs is sufficient, whereas in the former case inactivation of PBP 5 is necessary (after saturation of all other PBPs).
针对粪肠球菌野生型菌株以及在最适温度和次适温度下培养的三种超量产生PBP 5的突变体，评估了苄青霉素、氨苄青霉素、头孢噻肟和甲氧西林的最低抑菌浓度（MIC）和最低杀菌浓度（MBC）。在最适温度下生长的野生型菌株中，所有β-内酰胺类抗生素的MBC均显著高于MIC（抑菌作用）。与此相反，在次适温度下生长的相同细胞以及在所有温度下超量产生PBP 5的突变体中，所有抗生素的MIC均与MBC一致（杀菌作用）。在MIC和MBC相同的所有条件下，使用所有抗生素时，生长抑制仅在使所有青霉素结合蛋白（PBP）饱和的最低浓度（或更高浓度）下发生。相反，在MIC低于MBC的条件下，仅部分PBP在MIC和MBC时被饱和（或结合），PBP 5在任何情况下均未被饱和或结合。在生长抑制需要所有PBP饱和的所有条件下，细胞在所有抗生素的MBC时死亡，其动力学比在并非所有PBP都被饱和（或结合）的条件下在MBC时死亡的动力学要快得多。此外，在前一种条件下，高于MBC的抗生素浓度并未显著加速细胞死亡动力学，而在后一种条件下，随着抗生素浓度增加直至PBP完全饱和，动力学则会加速。有人提出，当所有PBP都被饱和时发生的杀菌作用是PBP功能失活的直接后果，而当只有部分PBP被饱和或结合时发生的杀菌作用也是（或主要是）细胞无法生长的间接后果，并且在粪肠球菌中，生长抑制和细胞杀伤的靶点存在于不同的PBP中：对于后一种作用，一种（或多种）高分子量PBP失活就足够了，而在前一种情况下，PBP 5失活是必要的（在所有其他PBP饱和之后）。
