Haycocks James R J, Sharma Prateek, Stringer Anne M, Wade Joseph T, Grainger David C
Institute of Microbiology and Infection, School of Biosciences, University of Birmingham, Edgbaston, Birmingham, United Kingdom.
Wadsworth Center, New York State Department of Health, Albany, New York, United States of America.
PLoS Pathog. 2015 Jan 8;11(1):e1004605. doi: 10.1371/journal.ppat.1004605. eCollection 2015 Jan.
Enterotoxigenic Escherichia coli (ETEC) cause severe diarrhoea in humans and neonatal farm animals. Annually, 380,000 human deaths, and multi-million dollar losses in the farming industry, can be attributed to ETEC infections. Illness results from the action of enterotoxins, which disrupt signalling pathways that manage water and electrolyte homeostasis in the mammalian gut. The resulting fluid loss is treated by oral rehydration. Hence, aqueous solutions of glucose and salt are ingested by the patient. Given the central role of enterotoxins in disease, we have characterised the regulatory trigger that controls toxin production. We show that, at the molecular level, the trigger is comprised of two gene regulatory proteins, CRP and H-NS. Strikingly, this renders toxin expression sensitive to both conditions encountered on host cell attachment and the components of oral rehydration therapy. For example, enterotoxin expression is induced by salt in an H-NS dependent manner. Furthermore, depending on the toxin gene, expression is activated or repressed by glucose. The precise sensitivity of the regulatory trigger to glucose differs because of variations in the regulatory setup for each toxin encoding gene.
产肠毒素大肠杆菌（ETEC）可导致人类和新生农场动物严重腹泻。每年，ETEC感染可导致38万人死亡，给养殖业造成数百万美元的损失。疾病是由肠毒素的作用引起的，肠毒素会破坏哺乳动物肠道中调节水和电解质平衡的信号通路。由此导致的体液流失通过口服补液进行治疗。因此，患者会摄入葡萄糖和盐的水溶液。鉴于肠毒素在疾病中的核心作用，我们已经确定了控制毒素产生的调节触发因素。我们发现，在分子水平上，触发因素由两种基因调节蛋白CRP和H-NS组成。令人惊讶的是，这使得毒素表达对宿主细胞附着时遇到的条件以及口服补液疗法的成分都敏感。例如，肠毒素表达以H-NS依赖的方式被盐诱导。此外，根据毒素基因的不同，表达会被葡萄糖激活或抑制。由于每个毒素编码基因的调节设置不同，调节触发因素对葡萄糖的精确敏感性也有所不同。
