Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, Charlottesville, VA, USA.
Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA.
Nat Commun. 2019 Apr 23;10(1):1826. doi: 10.1038/s41467-019-09808-4.
The bacterial pathogen Shigella flexneri causes 270 million cases of bacillary dysentery (blood in stool) worldwide every year, resulting in more than 200,000 deaths. A major challenge in combating bacillary dysentery is the lack of a small-animal model that recapitulates the symptoms observed in infected individuals, including bloody diarrhea. Here, we show that similar to humans, infant rabbits infected with S. flexneri experience severe inflammation, massive ulceration of the colonic mucosa, and bloody diarrhea. T3SS-dependent invasion of epithelial cells is necessary and sufficient for mediating immune cell infiltration and vascular lesions. However, massive ulceration of the colonic mucosa, bloody diarrhea, and dramatic weight loss are strictly contingent on the ability of the bacteria to spread from cell to cell. The infant rabbit model features bacterial dissemination as a critical determinant of S. flexneri pathogenesis and provides a unique small-animal model for research and development of therapeutic interventions.
细菌病原体福氏志贺菌每年在全球导致 2.7 亿例细菌性痢疾（粪便带血），导致超过 20 万人死亡。对抗细菌性痢疾的一个主要挑战是缺乏能够重现感染者（包括血性腹泻）观察到的症状的小动物模型。在这里，我们表明，感染福氏志贺菌的婴儿兔与人类相似，会经历严重的炎症、结肠黏膜的大规模溃疡和血性腹泻。T3SS 依赖性上皮细胞侵袭对于介导免疫细胞浸润和血管病变是必要且充分的。然而，结肠黏膜的大规模溃疡、血性腹泻和明显的体重减轻严格取决于细菌从一个细胞传播到另一个细胞的能力。婴儿兔模型的细菌传播是福氏志贺菌发病机制的关键决定因素，为研究和开发治疗干预措施提供了独特的小动物模型。
