Department of Biochemistry, University of Cambridge, UK.
Mol Microbiol. 2012 Feb;83(4):665-8. doi: 10.1111/j.1365-2958.2012.07974.x. Epub 2012 Jan 29.
Bacteria are constantly threatened by predation from bacteriophage parasites and, in response, have evolved an array of resistance mechanisms. These resistance mechanisms then place greater selection pressure on the infecting bacteriophages, which develop counter-strategies in a perpetual 'arms race' between virus and host. Toxin-antitoxin (TA) loci are widespread in bacteria and can confer multiple benefits, including resistance to bacteriophages. The study by Otsuka and Yonesaki, published in this issue of Molecular Microbiology, describes a new plasmid-encoded TA system, lsoAB, which confers resistance to a dmd(-) mutant of bacteriophage T4 through the activity of the LsoA toxin. Infections with wild-type T4, however, are unaffected as the Dmd protein acts as an alternative antitoxin to LsoA, thus preventing its anti-bacteriophage activity. Dmd has also been shown to negate the activity of a related toxin, RnlA. This is a striking result indicating that Dmd can act as a promiscuous antitoxin, binding and inhibiting multiple toxin partners, when antitoxin activity is generally considered to be limited to a single cognate toxin. This study is an exciting addition to both the bacteriophage resistance and TA fields, and suggests a greater role for TA system-based resistance and counter-resistance in the world's oldest predator-prey relationship.
细菌不断受到噬菌体寄生虫的捕食威胁,作为回应,它们进化出了一系列抵抗机制。这些抵抗机制进一步对感染的噬菌体施加了更大的选择压力,噬菌体在病毒和宿主之间的持续“军备竞赛”中发展出了对抗策略。毒素-抗毒素(TA)基因座广泛存在于细菌中,可以赋予多种益处,包括对噬菌体的抗性。Otsuka 和 Yonesaki 在本期《分子微生物学》上发表的研究描述了一种新的质粒编码 TA 系统 lsoAB,它通过 LsoA 毒素的活性赋予对噬菌体 T4 的 dmd(-)突变体的抗性。然而,野生型 T4 的感染不受影响,因为 Dmd 蛋白作为 LsoA 的替代抗毒素,从而阻止其抗噬菌体活性。Dmd 还被证明可以消除相关毒素 RnlA 的活性。这是一个惊人的结果,表明当抗毒素活性通常被认为仅限于单个同源毒素时,Dmd 可以作为一种混杂的抗毒素,结合并抑制多个毒素伴侣。这项研究是噬菌体抗性和 TA 领域的一个令人兴奋的补充,并表明基于 TA 系统的抗性和对抗抗性在世界上最古老的捕食者-猎物关系中发挥了更大的作用。