Eisenstein B I, Ofek I, Beachey E H
J Clin Invest. 1979 Jun;63(6):1219-28. doi: 10.1172/JCI109417.
When Escherichia coli was grown in sublethal concentrations of streptomycin, mannose binding activity and epithelial cell adherence of the E. coli cultures at stationary phase were significantly reduced in the drug-grown organisms. In a strain whose minimal inhibitory concentrations was 30 mug/ml, the percentage of reduction in mannose binding activity was dose related over a range of concentrations between 0.5 and 10 mug/ml streptomycin. Concomitant with the drug-induced suppression of mannose binding activity, antigenic and ultrastructural alterations on the surface of the drug-grown organisms were observed by agglutination tests and electron microscopy, respectively. The streptomycin effect was reversible, required actively growing organisms, and was most apparent in the early log-phase of growth. High doses of antibiotic were ineffective when added to cultures which had acquired mannose binding activity. An isogenic derivative with high-level resistance to streptomycin was obtained as a single-step mutation from the test E. coli strain. Whereas the isogenic mutant possessed mannose binding activity and adhering ability similar to the parent strain, it was resistant to the streptomycin-induced suppression of the two activities at enormous concentrations (up to 10,000 mug/ml) of streptomycin. Taken together the results suggest that the suppression of epithelial cell adherence and mannose binding activity of E. coli grown in sublethal concentrations of streptomycin is a result of classic mechanisms of drug action upon the bacterial ribosome. The results support the possibility that antibiotics may act through mechanisms other than inhibition of growth and bacterial killing to eradicate bacteria from mucosal surfaces.
当大肠杆菌在亚致死浓度的链霉素中生长时，处于稳定期的大肠杆菌培养物的甘露糖结合活性和上皮细胞黏附能力在经药物处理的菌体中显著降低。在一种最小抑菌浓度为30μg/ml的菌株中，在0.5至10μg/ml链霉素的浓度范围内，甘露糖结合活性的降低百分比与剂量相关。伴随着药物诱导的甘露糖结合活性抑制，分别通过凝集试验和电子显微镜观察到经药物处理的菌体表面的抗原性和超微结构改变。链霉素的作用是可逆的，需要活跃生长的菌体，并且在生长的对数早期最为明显。当添加到已获得甘露糖结合活性的培养物中时，高剂量抗生素无效。从测试的大肠杆菌菌株中通过单步突变获得了对链霉素具有高水平抗性的同基因衍生物。尽管同基因突变体具有与亲本菌株相似的甘露糖结合活性和黏附能力，但在高达10000μg/ml的链霉素高浓度下，它对链霉素诱导的这两种活性的抑制具有抗性。综合这些结果表明，在亚致死浓度的链霉素中生长的大肠杆菌的上皮细胞黏附能力和甘露糖结合活性的抑制是药物作用于细菌核糖体的经典机制的结果。这些结果支持了抗生素可能通过抑制生长和杀灭细菌以外的机制从黏膜表面清除细菌的可能性。
