Evolution of Copper Homeostasis and Virulence in Salmonella.

Evolution of Copper Homeostasis and Virulence in Salmonella.
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DOI:
10.3389/fmicb.2022.823176
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发表时间:
2022
影响因子:
5.2
通讯作者:
Soncini FC
Soncini FC
中科院分区:
生物学2区
文献类型:
--
作者:
Méndez AAE;Mendoza JI;Echarren ML;Terán I;Checa SK;Soncini FC

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肠道沙门氏菌鼠伤寒杆菌调节毒力所必需的因子的表达,有助于其在含沙门氏菌的液泡中抵抗铜(Cu)的激增而存活。这种杀菌性宿主先天免疫组分主要靶向细菌包膜,其中大多数铜蛋白被定位。虽然在大多数肠道物种的周质铜稳态维持的CusR/CusS控制的CusCFBA外排系统编码的cus基因座,我们注意到,这些基因从沙门氏菌核心基因组丢失。与此同时,沙门氏菌获得cueP,编码周质铜分子伴侣。作为cus,cueP被证明是在厌氧条件下的富铜环境中细菌生存所必需的,这表明它可以在功能上替代CusCFBA系统。在本研究中,将整个大肠杆菌cus基因座重新引入沙门氏菌野生型或ΔcueP菌株的染色体中。虽然集成的cus基因座没有影响铜耐氧条件下,它增加了铜耐性厌氧条件下,无论是否存在cueP。与Cus系统相反,CueP表达在高铜浓度下更高,并且随着时间的推移而持续,表明单独的功能。最后,我们观察到,无论cus的存在与否,cueP缺失的突变体与野生型菌株相比显示出巨噬细胞内复制的缺陷。我们的研究结果表明,CueP和CusCFBA发挥多余的功能,金属电阻,但不是细胞内的生存,因此,这种病原体的毒力。
Salmonella enterica sv. Typhimurium modulates the expression of factors essential for virulence, contributing to its survival against the surge of copper (Cu) in the Salmonella-containing vacuole. This bactericidal host innate immune component primarily targets the bacterial envelope, where most cuproproteins are localized. While in most enteric species periplasmic Cu homeostasis is maintained by the CusR/CusS-controlled CusCFBA efflux system encoded in the cus locus, we noticed that these genes were lost from the Salmonella-core genome. At the same time, Salmonella acquired cueP, coding for a periplasmic Cu chaperone. As cus, cueP was shown to be essential for bacterial survival in a copper-rich environment under anaerobiosis, suggesting that it can functionally substitute the CusCFBA system. In the present study, the whole Escherichia coli cus locus was reintroduced to the chromosome of the Salmonella wild-type or the ΔcueP strain. While the integrated cus locus did not affect Cu resistance under aerobic conditions, it increases Cu tolerance under anaerobiosis, irrespective of the presence or absence of cueP. In contrast to the Cus system, CueP expression is higher at high copper concentrations and persisted over time, suggesting separate functions. Finally, we observed that, regardless of the presence or absence of cus, a mutant deleted of cueP shows a deficiency in replication inside macrophages compared to the wild-type strain. Our results demonstrate that CueP and CusCFBA exert redundant functions for metal resistance, but not for intracellular survival, and therefore for the virulence of this pathogen.
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