Yang Ruixiang, Han Shuang, Yu Yanshuang, Li Hongru, Helmann John D, Schaufler Katharina, Johnson Michael D L, Yang Qiu E, Rensing Christopher
Institute of Environmental Microbiology, College of Resources and Environment, Fujian Agriculture and Forestry University, Fuzhou, Fujian, China.
Fujian Provincial Key Laboratory of Soil Environmental Health and Regulation, College of Resources and Environment, Fujian Agriculture and Forestry University, Fuzhou, Fujian, China.
Microbiol Spectr. 2025 Apr 9;13(5):e0263424. doi: 10.1128/spectrum.02634-24.
is widely recognized as a pathogen responsible for hospital-acquired infections and community-acquired invasive infections. It has rapidly become a significant global public health threat due to the emergence of hypervirulent and multidrug-resistant strains, which have increased the challenges associated with treating life-threatening infections. Tellurium resistance genes are widespread on virulence plasmids in isolates. However, the core function of the operon () in remains unclear. In this study, the multidrug-resistant P1927 strain was isolated from the sputum of a hospitalized pneumonia patient. The operon, along with antimicrobial resistance and virulence genes, was identified on a large hybrid plasmid in P1927. We generated a deletion mutant and demonstrated that this mutant exhibited reduced virulence in a larva infection model. Further physiological functional analysis revealed that is not only important for Te(IV) resistance but also for resistance to Zn(II), Mn(II), and phage infection. All genes of the operon were highly inducible by Zn(II), which is a stronger inducer than Te(IV), and the genes were also induced by Mn(II). Collectively, our study demonstrates novel physiological functions of TerC in Zn(II) resistance and virulence in .IMPORTANCE has rapidly become a global threat to public health. Although the operon is widely identified in clinical isolates, its physiological function remains unclear. It has been proposed that proteins encoded by the operon form a multi-site metal-binding complex, but its exact function is still unknown. TerC, a central component of the tellurium resistance determinant, was previously shown to interact with outer membrane proteins OmpA and KpsD in , suggesting potential changes in outer membrane structure and properties. Here, we report that TerC confers resistance to Zn(II), Mn(II), and phage infection, and Zn(II) was shown to be a strong inducer of the operon. Furthermore, TerC was identified as a novel virulence factor. Taken together, our results expand our understanding of the physiological functions encoded by the operon and its role in the virulence of , providing deeper insights into the link between heavy metal(loid) resistance determinants and virulence in pathogenic bacteria.
被广泛认为是医院获得性感染和社区获得性侵袭性感染的病原体。由于高毒力和多重耐药菌株的出现,它已迅速成为全球重大的公共卫生威胁,这增加了治疗危及生命的感染的相关挑战。碲抗性基因在分离株的毒力质粒上广泛存在。然而, 操纵子()在 中的核心功能仍不清楚。在本研究中,从一名住院肺炎患者的痰液中分离出多重耐药的 P1927 菌株。在 P1927 的一个大型杂交质粒上鉴定出了 操纵子以及抗菌抗性和毒力基因。我们构建了一个 缺失突变体,并证明该突变体在 幼虫感染模型中表现出毒力降低。进一步的生理功能分析表明, 不仅对 Te(IV) 抗性很重要,而且对 Zn(II)、Mn(II) 和噬菌体感染的抗性也很重要。 操纵子的所有基因都可被 Zn(II) 高度诱导,Zn(II) 是比 Te(IV) 更强的诱导剂, 基因也可被 Mn(II) 诱导。总体而言,我们的研究证明了 TerC 在 Zn(II) 抗性和 毒力方面的新生理功能。重要性已迅速成为对公共卫生的全球威胁。尽管 操纵子在临床分离株中被广泛鉴定,但其生理功能仍不清楚。有人提出, 操纵子编码的蛋白质形成多位点金属结合复合物,但其确切功能仍然未知。TerC 是碲抗性决定因素的核心成分,先前已证明它与 中的外膜蛋白 OmpA 和 KpsD 相互作用,表明外膜结构和性质可能发生变化。在这里,我们报告 TerC 赋予对 Zn(II)、Mn(II) 和噬菌体感染的抗性,并且 Zn(II) 被证明是 操纵子的强诱导剂。此外,TerC 被鉴定为一种新的毒力因子。综上所述,我们的结果扩展了我们对 操纵子编码的生理功能及其在 毒力中的作用的理解,为重金属(类金属)抗性决定因素与病原菌毒力之间的联系提供了更深入的见解。