Mourenza Álvaro, Gil José A, Mateos Luís M, Letek Michal
Department of Molecular Biology, Area of Microbiology, University of León, 24071 León, Spain.
Antioxidants (Basel). 2020 Jan 28;9(2):114. doi: 10.3390/antiox9020114.
is a facultative intracellular pathogen that causes infections in foals and many other animals such as pigs, cattle, sheep, and goats. Antibiotic resistance is rapidly rising in horse farms, which makes ineffective current antibiotic treatments based on a combination of macrolides and rifampicin. Therefore, new therapeutic strategies are urgently needed to treat infections caused by antimicrobial resistant strains. Here, we employed a mycoredoxinnull mutant strain highly susceptible to oxidative stress to screen for novel ROS-generating antibiotics. Then, we used the well-characterized Mrx1-roGFP2 biosensor to confirm the redox stress generated by the most promising antimicrobial agents identified in our screening. Our results suggest that different combinations of antibacterial compounds that elicit oxidative stress are promising anti-infective strategies against . In particular, the combination of macrolides with ROS-generating antimicrobial compounds such as norfloxacin act synergistically to produce a potent antibacterial effect against . Therefore, our screening approach could be applied to identify novel ROS-inspired therapeutic strategies against intracellular pathogens.
是一种兼性细胞内病原体，可导致马驹以及许多其他动物（如猪、牛、羊和山羊）感染。马场中抗生素耐药性正在迅速上升，这使得目前基于大环内酯类和利福平联合使用的抗生素治疗无效。因此，迫切需要新的治疗策略来治疗由抗菌耐药菌株引起的感染。在这里，我们使用了一种对氧化应激高度敏感的肌红氧化还原蛋白缺失突变菌株来筛选新型产生活性氧的抗生素。然后，我们使用特征明确的Mrx1-roGFP2生物传感器来确认我们筛选中鉴定出的最有前景的抗菌剂所产生的氧化还原应激。我们的结果表明，引发氧化应激的抗菌化合物的不同组合是对抗……的有前景的抗感染策略。特别是，大环内酯类与产生活性氧的抗菌化合物（如诺氟沙星）联合使用具有协同作用，可对……产生强大的抗菌效果。因此，我们的筛选方法可用于识别针对细胞内病原体的新型活性氧激发治疗策略。
