Martin-Luther-University Halle-Wittenberg, Institute for Biology/Microbiology, Molecular Microbiology, Halle, Germany.
J Bacteriol. 2023 Apr 25;205(4):e0034322. doi: 10.1128/jb.00343-22. Epub 2023 Mar 9.
Metal resistance of Cupriavidus metallidurans is based on determinants that were acquired in the past by horizontal gene transfer during evolution. Some of these determinants encode transmembrane metal efflux systems. Expression of most of the respective genes is controlled by two-component regulatory systems composed of a membrane-bound sensor/sensory histidine kinase (HK) and a cytoplasmic, DNA-binding response regulator (RR). Here, we investigated the interplay between the three closely related two-component regulatory systems CzcRS, CzcRS, and AgrRS. All three systems regulate the response regulator CzcR, while the RRs AgrR and CzcR were not involved in regulation. Target promoters were and for genes upstream and downstream of the central gene region. The two systems together repressed CzcRS-dependent upregulation of at low zinc concentrations in the presence of CzcS but activated this signal transmission at higher zinc concentrations. AgrRS and CzcRS interacted to quench CzcRS-mediated expression of and . Together, cross talk between the three two-component regulatory systems enhanced the capabilities of the Czc systems by controlling expression of the additional genes and . Bacteria are able to acquire genes encoding resistance to metals and antibiotics by horizontal gene transfer. To bestow an evolutionary advantage on their host cell, new genes must be expressed, and their expression should be regulated so that resistance-mediating proteins are produced only when needed. Newly acquired regulators may interfere with those already present in a host cell. Such an event was studied here in the metal-resistant bacterium Cupriavidus metallidurans. The results demonstrate how regulation by the acquired genes interacts with the host's extant regulatory network. This leads to emergence of a new system level of complexity that optimizes the response of the cell to periplasmic signals.
金属耐药的铜绿假单胞菌是基于在进化过程中通过水平基因转移获得的决定因素。其中一些决定因素编码跨膜金属外排系统。大多数相应基因的表达受由膜结合传感器/感觉组氨酸激酶（HK）和细胞质 DNA 结合反应调节剂（RR）组成的双组分调节系统控制。在这里，我们研究了三个密切相关的双组分调节系统 CzcRS、CzcRS 和 AgrRS 之间的相互作用。这三个系统都调节响应调节剂 CzcR，而 RR AgrR 和 CzcR 并未参与 调节。靶启动子为 和 ，分别位于中央 基因区域上下游的基因。在存在 CzcS 的情况下，两个系统一起在低锌浓度下抑制 CzcRS 依赖的 上调，但在较高锌浓度下激活这种信号传递。AgrRS 和 CzcRS 相互作用，抑制 CzcRS 介导的 和 的表达。三个双组分调节系统之间的交叉对话增强了 Czc 系统的能力，控制了额外基因 和 的表达。细菌能够通过水平基因转移获得编码金属和抗生素抗性的基因。为了使宿主细胞获得进化优势，新基因必须表达，并且它们的表达应该受到调控，以便只有在需要时才产生介导抗性的蛋白质。新获得的调节剂可能会干扰宿主细胞中已有的调节剂。在金属抗性细菌铜绿假单胞菌中研究了这种事件。结果表明了获得的基因的调节如何与宿主现存的调控网络相互作用。这导致了细胞对周质信号的反应出现了新的系统水平的复杂性，从而优化了细胞的反应。
