Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA.
Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, Colorado, USA.
Infect Immun. 2020 Dec 15;89(1). doi: 10.1128/IAI.00654-20.
is a Gram-negative bacterium and the causative agent of melioidosis. Despite advances in our understanding of the disease, poses a significant health risk, especially in regions of endemicity, where treatment requires prolonged antibiotic therapy. Even though the respiratory and percutaneous routes are well documented and considered the main ways to acquire the pathogen, the gastrointestinal tract is believed to be an underreported and underrecognized route of infection. In the present study, we describe the development of and models to study gastrointestinal infection. Further, we report that the type 6 secretion system (T6SS) and type 1 fimbriae are important virulence factors required for gastrointestinal infection. Using a human intestinal epithelial cell line and mouse primary intestinal epithelial cells (IECs), we demonstrated that adheres, invades, and forms multinucleated giant cells, ultimately leading to cell toxicity. We demonstrated that mannose-sensitive type 1 fimbria is involved in the initial adherence of to IECs, although the impact on full virulence was limited. Finally, we also showed that requires a functional T6SS for full virulence, bacterial dissemination, and lethality in mice infected by the intragastric route. Overall, we showed that is an enteric pathogen and that type 1 fimbria is important for intestinal adherence, and we identify a new role for T6SS as a key virulence factor in gastrointestinal infection. These studies highlight the importance of gastrointestinal melioidosis as an understudied route of infection and open a new avenue for the pathogenesis of .
是一种革兰氏阴性细菌，也是类鼻疽病的病原体。尽管我们对这种疾病的认识有所提高，但仍然构成重大的健康威胁，尤其是在流行地区，治疗需要长期使用抗生素。尽管呼吸道和皮肤途径已被充分记录并被认为是获得病原体的主要途径，但胃肠道被认为是感染的一个报道和认识不足的途径。在本研究中，我们描述了 和 模型的开发，以研究胃肠道感染。此外，我们报告称，VI 型分泌系统（T6SS）和 I 型菌毛是胃肠道感染所必需的重要毒力因子。我们使用人肠上皮细胞系和小鼠原代肠上皮细胞（IEC）证明了 黏附、入侵并形成多核巨细胞，最终导致细胞毒性。我们证明了甘露糖敏感型 I 型菌毛参与了 的初始黏附，尽管对完全毒力的影响有限。最后，我们还表明，通过胃肠道途径感染的小鼠中， 完全毒力、细菌播散和致死性需要功能性 T6SS。总的来说，我们表明 是一种肠道病原体，I 型菌毛对于 肠道黏附很重要，并且我们确定了 T6SS 在胃肠道感染中的一个新的毒力因子作用。这些研究强调了胃肠道类鼻疽作为一种研究不足的感染途径的重要性，并为 的发病机制开辟了新的途径。
