LIPOTEICHOIC ACID AS A NEW TARGET FOR ACTIVITY OF ANTIBIOTICS - MODE OF ACTION OF DAPTOMYCIN (LY146032)
LIPOTEICHOIC ACID AS A NEW TARGET FOR ACTIVITY OF ANTIBIOTICS - MODE OF ACTION OF DAPTOMYCIN (LY146032)
复制标题
DOI：
10.1128/aac.34.6.1220
复制
发表时间：
1990-06-01
影响因子：
4.9
通讯作者：
SATTA, G
中科院分区：
文献类型：
--
作者：
CANEPARI, P;BOARETTI, M;SATTA, G
达托霉素在MIC允许肠球菌菌株和枯草芽孢杆菌的细胞质量增加持续2至3小时，与对照组的速率相当。在此期间，前者的细胞形状改变为杆状构型，后者的细胞形状改变为长杆状。在这些细菌中，其中细胞质量继续增加，达托霉素的MIC抑制肽聚糖合成不超过20%，孵育20分钟后，约50%，孵育2小时后。其他大分子，如DNA，RNA和蛋白质，只受到轻微影响。相比之下，在MIC下用达托霉素处理20分钟后，在各种菌株中[14C]乙酸酯掺入脂质中减少了约50%。当详细评价主要的含脂质聚合物对合成的影响时，发现在肽聚糖和上述其它大分子仅被轻微抑制（20%）且总脂质合成被抑制50%的条件下，磷壁酸和脂磷壁酸的合成分别被抑制50%和93%。达托霉素未被发现进入细菌或哺乳动物细胞的细胞质。在只有钙离子存在的情况下，它与整个细菌细胞、细胞壁（包括含有和不含有膜的细胞壁）以及细菌和哺乳动物细胞的分离膜结合。用EDTA洗涤除去上述所有细胞和除细菌膜外的细胞级分中的达托霉素。结论：脂磷壁酸很可能是达托霉素的主要作用靶点。
Daptomycin at the MIC allowed the cell mass increase of enterococcal strains and Bacillus subtilis to continue for 2 to 3 h at rates comparable to those of the controls. During this time the cell shape of the former changed to a rod configuration and that of the latter changed to long rods. In these bacteria, in which cell mass continued to increase, the MIC of daptomycin inhibited peptidoglycan synthesis by no more than 20% after 20 min of incubation and by roughly 50% after 2 h of incubation. Other macromolecules, such as DNA, RNA, and proteins, were only slightly affected. In contrast, incorporation of [14C]acetate into lipids was reduced by about 50% in the various strains after 20 min of treatment with daptomycin at the MIC. When the effect of the major lipid-containing polymers on synthesis was evaluated in detail, it was found that under conditions in which peptidoglycan and the other macromolecular mentioned above were inhibited only slightly (20%) and total lipid synthesis was inhibited by 50%, synthesis of teichoic and lipoteichoic acids was inhibited by 50 and 93%, respectively. Daptomycin was not found to enter the cytoplasm of either bacterial or mammalian cells. It bound, in the presence of calcium ions only, to whole bacterial cells, cell walls (both those that contained and those that did not contain membranes), and isolated membranes of bacterial and mammalian cells. Washing with EDTA removed daptomycin from all cells mentioned above and cell fractions except the bacterial membrane. It is concluded that lipoteichoic acid is most likely the primary target of daptomycin.