Lehrstuhl für Mikrobiologie, Universität Würzburg, Würzburg, Germany.
Int J Antimicrob Agents. 1993;2(4):263-70. doi: 10.1016/0924-8579(93)90060-i.
S fimbrial adhesins (Sfa) represent virulence factors of E. coli wild-type strains causing urinary tract infections and meningitis of the new born. In order to determine the influence of subinhibitory concentration of antibiotics on the expression of the sfa gene cluster, a wild-type strain carrying the lacZ gene, coding for the enzyme beta-galactosidase fused to the sfa determinant was used. The expression of lacZ which was under the control of the sfa wild-type promoters, was now equivalent to the sfa gene expression of wild-type strain 536. With this strain the influence of subinhibitory concentrations of 28 antibiotics on the expression of the sfa determinant was studied. The expression was strongly suppressed by a treatment of the wild-type fusion strain by aztreonam, gentamicin, clindamycin and trimethoprim; the latter had a dramatic effect on sfa expression. It was further shown for clindamycin and trimethoprim that the reduction of sfa gene expression was dependent on the concentration of the antibiotics. In contrast imipinem, amphotericin B and rifampicin weakly stimulated sfa expression. We conclude that gene fusions between virulence-associated loci and indicator genes in wild-type pathogens are useful to study virulence modulation due to subinhibitory concentration of antibiotics on the genetic level.
菌毛粘附素（Sfa）是引起尿路感染和新生儿脑膜炎的大肠杆菌野生型菌株的毒力因子。为了确定亚抑菌浓度抗生素对 sfa 基因簇表达的影响，使用携带 lacZ 基因的野生型菌株，该基因编码与 sfa 决定簇融合的β-半乳糖苷酶。受 sfa 野生型启动子控制的 lacZ 表达现在相当于野生型菌株 536 的 sfa 基因表达。利用该菌株，研究了 28 种抗生素的亚抑菌浓度对 sfa 决定簇表达的影响。亚抑菌浓度的氨曲南、庆大霉素、克林霉素和甲氧苄啶处理野生型融合株强烈抑制 sfa 决定簇的表达；后者对 sfa 表达有显著影响。进一步表明，克林霉素和甲氧苄啶对 sfa 基因表达的降低依赖于抗生素的浓度。相比之下，亚抑菌浓度的两性霉素 B 和利福平弱刺激 sfa 表达。我们得出结论，在野生型病原体中，毒力相关基因座与指示剂基因之间的基因融合对于研究由于抗生素的亚抑菌浓度而导致的毒力调节在遗传水平上是有用的。
