Department of Biochemistry, Tennis Court Road, Cambridge, CB2 1QW, UK.
FEMS Microbiol Lett. 2018 Jul 1;365(13). doi: 10.1093/femsle/fny134.
Ciprofloxacin is one of the most widely-used antibiotics, and has proven especially effective at controlling infections associated with the opportunistic human pathogen, Pseudomonas aeruginosa. In this work, we show that sub-inhibitory concentrations of ciprofloxacin induce discrete changes in the intracellular proteome. Central metabolism and cell envelope-associated functions are particularly affected. In spite of the low magnitude of the intracellular proteomic changes, we found that sub-lethal concentrations of ciprofloxacin had substantial effects on motility and exoprotein secretion. Crucially, the proteomic and phenotypic modulations that we observed were absolutely dependent upon the presence of wild-type GyrA; an isogenic strain of P. aeruginosa carrying a ciprofloxacin-insensitive form of GyrA (a T83→I mutant) did not display ciprofloxacin-dependent changes unless complemented with wild-type gyrA in trans. These results show that the diverse effects of sub-inhibitory ciprofloxacin on the cell are routed through its primary target in the cell, DNA gyrase.
环丙沙星是应用最广泛的抗生素之一，已被证明对控制机会性病原体铜绿假单胞菌感染特别有效。在这项工作中，我们表明，亚抑制浓度的环丙沙星会引起细胞内蛋白质组的离散变化。中心代谢和细胞包膜相关功能受到特别影响。尽管细胞内蛋白质组变化的幅度很小，但我们发现亚致死浓度的环丙沙星对运动和外蛋白分泌有很大的影响。至关重要的是，我们观察到的蛋白质组和表型调节完全依赖于野生型 GyrA 的存在；铜绿假单胞菌的一个同工型菌株携带一种环丙沙星不敏感的 GyrA 形式（T83→I 突变），除非在转座中补充野生型 gyrA，否则不会显示出依赖于环丙沙星的变化。这些结果表明，亚抑制浓度的环丙沙星对细胞的多种影响是通过其在细胞中的主要靶标 DNA 回旋酶来实现的。
