Baylor College of Medicine, Department of Molecular Virology and Microbiology, One Baylor Plaza, Houston, Texas 77030, USA.
University of Oregon, Institute for Molecular Biology, 1318 Franklin Boulevard, Eugene, Oregon 97403, USA.
Nature. 2018 Jan 18;553(7688):291-294. doi: 10.1038/nature25178. Epub 2018 Jan 3.
Clostridium difficile disease has recently increased to become a dominant nosocomial pathogen in North America and Europe, although little is known about what has driven this emergence. Here we show that two epidemic ribotypes (RT027 and RT078) have acquired unique mechanisms to metabolize low concentrations of the disaccharide trehalose. RT027 strains contain a single point mutation in the trehalose repressor that increases the sensitivity of this ribotype to trehalose by more than 500-fold. Furthermore, dietary trehalose increases the virulence of a RT027 strain in a mouse model of infection. RT078 strains acquired a cluster of four genes involved in trehalose metabolism, including a PTS permease that is both necessary and sufficient for growth on low concentrations of trehalose. We propose that the implementation of trehalose as a food additive into the human diet, shortly before the emergence of these two epidemic lineages, helped select for their emergence and contributed to hypervirulence.
艰难梭菌疾病最近在北美和欧洲已成为一种主要的医院获得性病原体，尽管人们对导致这种出现的原因知之甚少。在这里，我们表明，两种流行的核糖体型（RT027 和 RT078）已经获得了独特的机制来代谢低浓度的二糖海藻糖。RT027 菌株在海藻糖阻遏物中含有一个单点突变，使该核糖体型对海藻糖的敏感性增加了 500 多倍。此外，饮食中的海藻糖增加了 RT027 菌株在感染小鼠模型中的毒力。RT078 菌株获得了一组涉及海藻糖代谢的四个基因，包括 PTS 渗透酶，该酶对于在低浓度的海藻糖上生长是必需且充分的。我们提出，在这两个流行谱系出现前不久，将海藻糖作为食品添加剂实施到人类饮食中，有助于选择它们的出现，并导致它们的高毒力。
