Department of Cell and Molecular Biology, Uppsala University, Uppsala, Sweden.
PLoS Genet. 2020 Feb 13;16(2):e1008607. doi: 10.1371/journal.pgen.1008607. eCollection 2020 Feb.
RHS elements are components of conserved toxin-delivery systems, wide-spread within the bacterial kingdom and some of the most positively selected genes known. However, very little is known about how Rhs toxins affect bacterial biology. Salmonella Typhimurium contains a full-length rhs gene and an adjacent orphan rhs gene, which lacks the conserved delivery part of the Rhs protein. Here we show that, in addition to the conventional delivery, Rhs toxin-antitoxin pairs encode for functional type-II toxin-antitoxin (TA) loci that regulate S. Typhimurium proliferation within macrophages. Mutant S. Typhimurium cells lacking both Rhs toxins proliferate 2-times better within macrophages, mainly because of an increased growth rate. Thus, in addition to providing strong positive selection for the rhs loci under conditions when there is little or no toxin delivery, internal expression of the toxin-antitoxin system regulates growth in the stressful environment found inside macrophages.
RHS 元件是保守的毒素输送系统的组成部分，广泛存在于细菌界，是已知的最受正向选择的基因之一。然而，关于 Rhs 毒素如何影响细菌生物学，我们知之甚少。鼠伤寒沙门氏菌含有全长的 rhs 基因和相邻的孤儿 rhs 基因，后者缺乏 Rhs 蛋白保守的输送部分。在这里，我们表明，除了常规输送，Rhs 毒素-抗毒素对编码功能性 II 型毒素-抗毒素（TA）基因座，调节沙门氏菌在巨噬细胞内的增殖。缺乏两种 Rhs 毒素的鼠伤寒沙门氏菌突变细胞在巨噬细胞内的增殖能力提高了 2 倍，主要是因为生长速度加快。因此，除了在毒素输送很少或没有的情况下为 rhs 基因座提供强大的正向选择外，毒素-抗毒素系统的内部表达还调节了在巨噬细胞内发现的应激环境中的生长。
