Cialdella J I, Ulrich R G, Liggett W F, Adams L D, Marshall V P
Chemical & Biological Screening, Upjohn Company, Kalamazoo, Michigan 49001.
Antimicrob Agents Chemother. 1990 Nov;34(11):2086-92. doi: 10.1128/AAC.34.11.2086.
Trospectomycin sulfate, a chemically synthesized analog of spectinomycin, exhibits a broad range of activity against both aerobes and anaerobes, including the etiological agents of sexually transmitted diseases. Its activity in vitro against Escherichia coli is considered only moderate. At subinhibitory levels, however, trospectomycin induced changes in a pathogenic strain of E. coli, UC 9451, which significantly increased its sensitivity to serum lysis. This strain of E. coli shows high-level resistance to serum in vitro, typically growing twofold within a 45-min incubation period. Following exposure to one-fifth the MIC of trospectomycin, greater than 99% of the bacteria were killed in 25% serum within 15 min. Surviving bacteria were static in this level of serum for over 3 h. Killing was due to lysis mediated by both the classical and alternative complement pathways. The bacteria exposed to trospectomycin were enlarged in both diameter and length, but they still grew at rates comparable to those of untreated bacteria. No other visible morphological changes could be directly related to the increase in serum sensitivity. The profile of outer membrane proteins obtained by sodium dodecyl sulfate-polyacrylamide gel electrophoresis was identical for trospectomycin-treated or untreated bacteria. However, the relative proportion of four major outer membrane proteins varied considerably.
硫酸曲古霉素是壮观霉素的化学合成类似物,对需氧菌和厌氧菌均具有广泛的活性,包括性传播疾病的病原体。其体外对大肠杆菌的活性仅被认为是中等的。然而,在亚抑制水平下,曲古霉素可诱导致病性大肠杆菌菌株UC 9451发生变化,显著提高其对血清溶解的敏感性。该大肠杆菌菌株在体外对血清表现出高水平抗性,通常在45分钟的孵育期内数量增加一倍。在接触五分之一最小抑菌浓度的曲古霉素后,超过99%的细菌在15分钟内在25%血清中被杀死。存活的细菌在这种血清水平下静止超过3小时。杀菌是由经典和替代补体途径介导的溶解所致。暴露于曲古霉素的细菌在直径和长度上均增大,但它们的生长速度仍与未处理的细菌相当。没有其他可见的形态学变化可直接与血清敏感性的增加相关。通过十二烷基硫酸钠-聚丙烯酰胺凝胶电泳获得的外膜蛋白图谱,经曲古霉素处理或未处理的细菌是相同的。然而,四种主要外膜蛋白的相对比例有很大差异。