Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, One Shields Avenue, Davis, CA 95616, USA.
Department of Chemistry, College of Letters and Sciences, University of California, Davis, One Shields Avenue, Davis, CA 95616, USA.
Cell Host Microbe. 2018 Feb 14;23(2):266-273.e4. doi: 10.1016/j.chom.2018.01.004.
Salmonella enterica serovar (S.) Typhi is an extraintestinal pathogen that evolved from Salmonella serovars causing gastrointestinal disease. Compared with non-typhoidal Salmonella serovars, the genomes of typhoidal serovars contain various loss-of-function mutations. However, the contribution of these genetic differences to this shift in pathogen ecology remains unknown. We show that the ydiQRSTD operon, which is deleted in S. Typhi, enables S. Typhimurium to utilize microbiota-derived butyrate during gastrointestinal disease. Unexpectedly, genetic ablation of butyrate utilization reduces S. Typhimurium epithelial invasion and attenuates intestinal inflammation. Deletion of ydiD renders S. Typhimurium sensitive to butyrate-mediated repression of invasion gene expression. Combined with the gain of virulence-associated (Vi) capsular polysaccharide and loss of very-long O-antigen chains, two features characteristic of S. Typhi, genetic ablation of butyrate utilization abrogates S. Typhimurium-induced intestinal inflammation. Thus, the transition from a gastrointestinal to an extraintestinal pathogen involved discrete genetic changes, providing insights into pathogen evolution and emergence.
肠道外病原体沙门氏菌血清型 Typhi 是由引起胃肠道疾病的沙门氏菌血清型进化而来的。与非伤寒型沙门氏菌血清型相比，伤寒型血清型的基因组包含各种功能丧失突变。然而，这些遗传差异对这种病原体生态系统转变的贡献尚不清楚。我们表明，在 S. Typhi 中缺失的 ydiQRSTD 操纵子使 S. Typhimurium 能够在胃肠道疾病期间利用微生物群衍生的丁酸盐。出乎意料的是，丁酸利用的遗传缺失会降低 S. Typhimurium 的上皮侵袭并减弱肠道炎症。ydiD 的缺失使 S. Typhimurium 对丁酸盐介导的侵袭基因表达抑制敏感。与获得与毒力相关的（Vi）荚膜多糖和失去非常长的 O-抗原链相结合，这是 S. Typhi 的两个特征，丁酸利用的遗传缺失消除了 S. Typhimurium 引起的肠道炎症。因此，从胃肠道病原体到肠道外病原体的转变涉及离散的遗传变化，为病原体的进化和出现提供了新的视角。
