Salmonella enterica serovar Typhimurium pathogenicity island 2 is necessary for complete virulence in a mouse model of infectious enterocolitis
Salmonella enterica serovar Typhimurium pathogenicity island 2 is necessary for complete virulence in a mouse model of infectious enterocolitis
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DOI：
10.1128/iai.73.6.3219-3227.2005
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发表时间：
2005-06-01
影响因子：
3.1
通讯作者：
Finlay, BB
中科院分区：
文献类型：
--
作者：
Coburn, B;Li, YL;Finlay, BB
沙门氏菌在多种宿主中引起多种疾病。肠沙门氏菌鼠伤寒血清型会导致人类自限性肠道疾病和易感小鼠的全身伤寒样疾病。鼠伤寒沙门氏菌致病机制中普遍存在的教条是，不同的毒力机制 - 沙门氏菌致病性岛 1 和 2（SPI1 和 SPI2） - 在发病机制中发挥不同的作用，前者对于侵袭和肠道疾病很重要，后者对于细胞内存活和全身持久性和疾病很重要。尽管来自牛感染的证据表明 SPI2 在回肠疾病中发挥作用，但没有证据表明 SPI2 对于更接近人类结肠炎的疾病的炎症很重要。使用缺乏功能性 III 型分泌系统的鼠伤寒沙门氏菌菌株，我们证明 SPI2 对于鼠传染性小肠结肠炎的完全毒力至关重要。使用最近表征的小鼠模型（M. Barthel，S. Hapfelmeier，L. Quintanilla-Martinez，M. Kremer，M. Rohde，M. Hogardt，K. Pfeffer，H. Russmann 和 W. D. Hardt，Infect. Immun. 71：2839-2858，2003），我们证明 SPI1 突变体无法引起肠道疾病 48 小时感染后，SPI2 缺陷细菌也会引起显着的减毒盲肠炎。我们发现，在盲肠炎症高峰期，SPI2 突变体诱导细胞间粘附分子 I 表达和中性粒细胞募集减少，但野生型和突变型沙门氏菌在受感染器官的管腔中分布相似。最后，我们证明，在突变型而非野生型感染中，肠道炎症的减弱伴随着伤寒的消退。总的来说，这些结果表明 SPI2 是小肠结肠炎以及全身性疾病所必需的。
Salmonella species cause a wide range of disease in multiple hosts. Salmonella enterica serovar Typhimurium causes self-limited intestinal disease in humans and systemic typhoid-like illness in susceptible mice. The prevailing dogma in murine S. enterica serovar Typhimurium pathogenesis is that distinct virulence mechanisms - Salmonella pathogenicity islands 1 and 2 (SPI1 and SPI2) - perform distinct roles in pathogenesis, the former being important for invasion and intestinal disease and the latter important for intracellular survival and systemic persistence and disease. Although evidence from bovine infections has suggested that SPI2 has a role in ileal disease, there is no evidence that SPI2 is important for inflammation in a disease that more closely recapitulates human colitis. Using S. enterica serovar Typhimurium strains that lack functional type III secretion systems, we demonstrate that SPI2 is essential for complete virulence in murine infectious enterocolitis. Using a recently characterized murine model (M. Barthel,S. Hapfelmeier, L. Quintanilla-Martinez, M. Kremer, M. Rohde, M. Hogardt, K. Pfeffer, H. Russmann, and W. D. Hardt, Infect. Immun. 71:2839-2858, 2003), we demonstrate that SPI1 mutants are unable to cause intestinal disease 48 h after infection and that SPI2-deficient bacteria also cause significantly attenuated typhlitis. We show that at the peak of inflammation in the cecum, SPI2 mutants induce diminished intercellular adhesion molecule I expression and neutrophil recruitment but that wild-type and mutant Salmonella are similarly distributed in the lumen of the infected organ. Finally, we demonstrate that attenuation of intestinal inflammation is accompanied by resolution of typhlitis in the mutant, but not wild-type, infections. Collectively, these results indicate that SPI2 is needed for enterocolitis, as well as for systemic disease.