Institute of Nanotechnology and Advanced Materials & Department of Chemistry, Faculty of Exact Sciences, Bar-Ilan University, Ramat-Gan 5290002, Israel.
Int J Mol Sci. 2021 Feb 19;22(4):2050. doi: 10.3390/ijms22042050.
Thirty-five thousand people die as a result of more than 2.8 million antibiotic-resistant infections in the United States of America per year. () is classified a serious threat, the second-highest threat category of the U.S. Department of Health and Human Services. Among others, the World Health Organization (WHO) encourages the discovery and development of novel antibiotic classes with new targets and mechanisms of action without cross-resistance to existing classes. To find potential new target sites in pathogenic bacteria, such as , it is inevitable to fully understand the molecular mechanism of homeostasis, metabolism, regulation, growth, and resistances thereof. maintains a sophisticated copper defense cascade comprising three stages, resembling those of public safety organizations. These stages include copper scavenging, first responder, and second responder. Similar mechanisms are found in numerous pathogens. Here we compare the copper-dependent transcription regulators cueR and copRS of () and . Further, phylogenetic analysis and structural modelling of mexPQ-opmE reveal that this efflux pump is unlikely to be involved in the copper export of . Altogether, we present current understandings of the copper homeostasis in and potential new target sites for antimicrobial agents or a combinatorial drug regimen in the fight against multidrug resistant pathogens.
每年有 3.5 万人因美国超过 280 万例抗生素耐药性感染而死亡。（ ）被归类为严重威胁，是美国卫生与公众服务部的第二高威胁类别。世界卫生组织（WHO）除其他外，鼓励发现和开发具有新靶标和作用机制的新型抗生素类别，避免与现有类别产生交叉耐药性。为了在致病菌中找到潜在的新靶标位点，例如（ ），全面了解其体内平衡、代谢、调节、生长和耐药性的分子机制是必不可少的。（ ）维持着一个复杂的铜防御级联反应，包括三个阶段，类似于公共安全组织的阶段。这些阶段包括铜的清除、第一反应者和第二反应者。类似的机制在许多病原体中都有发现。在这里，我们比较了（ ）和（ ）的铜依赖性转录调节因子 cueR 和 copRS。此外，mexPQ-opmE 的系统发育分析和结构建模表明，该外排泵不太可能参与（ ）的铜输出。总之，我们介绍了（ ）中铜稳态的现有认识以及针对抗药性病原体的抗菌剂或组合药物治疗的潜在新靶标位点。
