Iacobino Angelo, Piccaro Giovanni, Pardini Manuela, Fattorini Lanfranco, Giannoni Federico
Dipartimento di Malattie Infettive, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
Organismo Notificato Unificato, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
Microorganisms. 2021 Jan 27;9(2):255. doi: 10.3390/microorganisms9020255.
Previous studies on demonstrated that sub-minimum inhibitory concentration (MIC) of fluoroquinolones induced the SOS response, increasing drug tolerance. We characterized the transcriptional response to moxifloxacin in . Reference strain H37Rv was treated with moxifloxacin and gene expression studied by qRT-PCR. Five SOS regulon genes, , , , and were induced in a dose- and time-dependent manner. A range of moxifloxacin concentrations induced , with a peak observed at 2 × MIC (0.25 μg/mL) after 16 h. Another seven SOS responses and three DNA repair genes were significantly induced by moxifloxacin. Induction of by moxifloxacin was higher in log-phase than in early- and stationary-phase cells, and absent in dormant bacilli. Furthermore, in an H37Rv fluoroquinolone-resistant mutant carrying the D94G mutation in the gene, the SOS response was induced at drug concentrations higher than the mutant MIC value. The 2 × MIC of moxifloxacin determined no significant changes in gene expression in a panel of 32 genes, except for up-regulation of the toxin and of and , two persistence-related genes. Overall, our data show that activation of the SOS response by moxifloxacin, a likely link to increased mutation rate and persister formation, is time, dose, physiological state and, possibly, MIC dependent.
先前关于……的研究表明，氟喹诺酮类药物的亚最小抑菌浓度（MIC）可诱导SOS反应，增加耐药性。我们对……中莫西沙星的转录反应进行了表征。用莫西沙星处理参考菌株H37Rv，并通过qRT-PCR研究基因表达。五个SOS调控子基因，……、……、……、……和……以剂量和时间依赖性方式被诱导。一系列莫西沙星浓度均可诱导……，在16小时后2×MIC（0.25μg/mL）时观察到峰值。另外七个SOS反应和三个DNA修复基因也被莫西沙星显著诱导。莫西沙星对……的诱导在对数期高于早期和稳定期细胞，而在休眠芽孢杆菌中不存在。此外，在携带……基因D94G突变的H37Rv氟喹诺酮耐药突变体中，在药物浓度高于突变体MIC值时诱导了SOS反应。莫西沙星的2×MIC在一组32个基因中未引起基因表达的显著变化，除了……毒素以及两个与持续存在相关的基因……和……的上调。总体而言，我们的数据表明，莫西沙星激活SOS反应，这可能与突变率增加和持续菌形成有关，是时间、剂量、生理状态以及可能与MIC相关的。
