Enterohemorrhagic Escherichia coli is a significant human pathogen that causes disease ranging from hemorrhagic colitis to hemolytic uremic syndrome. The latter can lead to potentially fatal renal failure and is caused by the release of Shiga toxins that are encoded within lambdoid bacteriophages. The toxins are encoded within the late transcript of the phage and are regulated by antitermination of the P_R′ late promoter during lytic induction of the phage. During lysogeny, the late transcript is prematurely terminated at t_R′ immediately downstream of P_R′, generating a short RNA that is a byproduct of antitermination regulation. We demonstrate that this short transcript binds the small RNA chaperone Hfq, and is processed into a stable 74-nt regulatory small RNA that we have termed StxS. StxS represses expression of Shiga toxin 1 under lysogenic conditions through direct interactions with the stx1AB transcript. StxS acts in trans to activate expression of the general stress response sigma factor, RpoS, through direct interactions with an activating seed sequence within the 5′ UTR. Activation of RpoS promotes high cell density growth under nutrient-limiting conditions. Many phages utilize antitermination to regulate the lytic/lysogenic switch and our results demonstrate that short RNAs generated as a byproduct of this regulation can acquire regulatory small RNA functions that modulate host fitness.

肠出血性大肠杆菌是一种重要的人类病原体，其引起的疾病范围从出血性结肠炎到溶血性尿毒症综合征。后者可能导致潜在的致命性肾功能衰竭，并且是由Lambdoid噬菌体中编码的志贺毒素的释放引起的。毒素被编码在噬菌体的晚期转录物中，并在裂解诱导噬菌体期间通过P _R'晚期启动子的抗终止来调节。在溶菌原过程中，晚期转录物在t _R'处提前终止于P _R'的下游，产生的短RNA是抗终止调节的副产物。我们证明了此短转录本结合小分子分子伴侣Hfq，并被加工成稳定的74 nt调控小分子RNA，我们称之为StxS。StxS通过与stx1AB转录本直接相互作用，在溶原性条件下抑制志贺毒素1的表达。StxS反式作用通过与5'UTR内的激活种子序列直接相互作用来激活一般应激反应sigma因子RpoS的表达。RpoS的激活在营养限制条件下促进高细胞密度生长。许多噬菌体利用抗终止来调节裂解/溶原性转换，我们的结果表明，作为该调节副产物产生的短RNA可以获得调节宿主适应性的调节性小RNA功能。