Matera G, Berlinghieri M C, Barreca G, Focà A
Dipartimento di Scienze Microbiologiche, Neurologiche, Ortopediche, Catanzaro, Italy.
New Microbiol. 1995 Jul;18(3):325-9.
Four novel glycopeptide antibiotics, namely MDL 62708, MDL 63155, MDL 62827, MDL 62873 (mideplanin), plus teicoplanin, which differ in their chemical structure, were used to examine the relationship between the structure of glycopeptides and their LPS neutralization activity. Compound MDL 62708 (100 micrograms/ml) significantly reduced (P < 0.01 vs. antibiotic-free LPS, by Fisher's PLSD Test) metachromatic reactivity of S. minnesota R595 LPS (500 micrograms/ml) as evaluated by the DMB test. The remaining glycopeptides showed a significant reduction of the metachromatic reactivity, although at concentrations (333 and 1000 micrograms/ml) higher than MDL 62708. Data obtained with LAL test appeared in accordance with those of the other techniques: all the glycopeptides used (100 and 1000 micrograms/ml) significantly (P < 0.05) reduced the reactivity of S. minnesota R595 LPS (50 pg/ml), and the lowest concentration of MDL 62708 (10 pg/ml) used produced a substantial, although not significant, reduction of the LPS reactivity with LAL. The antibiotic/LPS ratios associated to a significant reduction of LPS reactivity were 3.3/5 (wt/wt) and 2/1 (wt/wt) for DMB and LAL tests respectively. Such ratio appeared to be even lower for MDL 62708. In conclusion, the four new glycopeptides, when tested at an antibiotic/LPS ratio about 1000 times lower than that which can be found in vivo, were able to reduce the reactivity of LPS in the in vitro models used. Teicoplanin aglycone MDL 62708, which also lacks the teicoplanin fatty acid, seems to have the same anti-LPS activity as the parental antibiotic, thus suggesting an important role for the glycopeptide backbone and NH2 groups in LPS-neutralizing effect.
四种新型糖肽类抗生素，即MDL 62708、MDL 63155、MDL 62827、MDL 62873（米德普拉宁），再加上替考拉宁，它们的化学结构各不相同，被用于研究糖肽结构与其脂多糖中和活性之间的关系。化合物MDL 62708（100微克/毫升）通过二甲基甲酰胺（DMB）试验评估，显著降低了（通过Fisher氏PLSD检验，与无抗生素的明尼苏达R595脂多糖相比，P<0.01）浓度为500微克/毫升的明尼苏达R595脂多糖的异染反应性。其余糖肽类抗生素虽然浓度（333和1000微克/毫升）高于MDL 62708，但也显著降低了异染反应性。用鲎试剂（LAL）试验获得的数据与其他技术的数据一致：所有使用的糖肽（100和1000微克/毫升）均显著（P<0.05）降低了浓度为50皮克/毫升的明尼苏达R595脂多糖的反应性，并且所使用的MDL 62708的最低浓度（10皮克/毫升）虽然未达到显著水平，但也使脂多糖与鲎试剂的反应性大幅降低。对于DMB试验和LAL试验，与脂多糖反应性显著降低相关的抗生素/脂多糖比例分别为3.3/5（重量/重量）和2/1（重量/重量）。对于MDL 62708，该比例似乎更低。总之，这四种新的糖肽类抗生素在以比体内所能发现的比例低约1000倍的抗生素/脂多糖比例进行测试时，能够降低所使用的体外模型中脂多糖的反应性。替考拉宁苷元MDL 62708，其也缺乏替考拉宁脂肪酸，似乎具有与母体抗生素相同的抗脂多糖活性，因此表明糖肽主链和氨基在脂多糖中和作用中起重要作用。
