Centre for Chemical Biology, Universiti Sains Malaysia, Penang, Malaysia; Universiti Sultan Zainal Abidin Teaching Hospital, Terengganu, Malaysia.
Institute for Research in Molecular Medicine, Universiti Sains Malaysia, Penang, Malaysia.
Int J Biol Macromol. 2022 Oct 31;219:1080-1086. doi: 10.1016/j.ijbiomac.2022.08.144. Epub 2022 Aug 24.
The RelEB3 toxin-antitoxin (TA) system of Salmonella enterica subsp. enterica serovar Typhimurium consists of a RelE3 toxin which suppresses bacterial growth, but its RelB3 antitoxin does not neutralise the toxin. The relEB3 operon is widespread in Proteobacteria and is related to higBA2 from Vibrio cholerae. In contrast to the ribosome-dependent HigB2 toxin, however, the RelE3 toxin degraded free RNA independently of the ribosome. A basic loop possibly involved in HigB2's binding to the ribosome is shortened in RelE3, which instead contains a uniquely conserved R51 important for RelE3's toxicity. The RelB3 antitoxin, meanwhile, specifically recognised the CACCTGGTG palindromic motif in the promoter site. RelB3 contains a unique P14 which is conserved as Ala in most homologues, and mutating P14 to Ala enabled the antitoxin to bind to RelE3 and restored bacterial growth. The P14 RelB3 variant, which most likely arose by a point mutation in a recent ancestor of S. Typhimurium and closely related serovars, could have possibly provided the bacteria with a faster response to stress, and might have spread to other serovars through homologous recombination.
鼠伤寒沙门氏菌亚种肠炎血清型的 RelEB3 毒素-抗毒素（TA）系统由 RelE3 毒素组成，该毒素抑制细菌生长，但它的 RelB3 抗毒素不能中和毒素。relEB3 操纵子广泛存在于变形菌门中，与霍乱弧菌的 higBA2 有关。然而，与依赖核糖体的 HigB2 毒素不同，RelE3 毒素独立于核糖体降解游离 RNA。可能与 HigB2 结合核糖体有关的碱性环在 RelE3 中缩短，而 RelE3 中则包含一个独特保守的 R51，这对于 RelE3 的毒性很重要。同时，RelB3 抗毒素特异性识别启动子位点上的 CACCTGGTG 回文基序。RelB3 含有一个独特的 P14，在大多数同源物中为 Ala 保守，将 P14 突变为 Ala 使抗毒素能够与 RelE3 结合并恢复细菌生长。P14 RelB3 变体很可能是鼠伤寒沙门氏菌及其密切相关血清型的最近祖先中的点突变产生的，它可能为细菌提供了对压力更快的反应，并可能通过同源重组传播到其他血清型。
