State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, China.
Key Laboratory of Bio-resources and Eco-environment, Ministry of Education, College of Life Sciences, Sichuan University, Chengdu, China.
Nat Microbiol. 2019 Mar;4(3):459-469. doi: 10.1038/s41564-018-0322-4. Epub 2019 Jan 7.
Pseudomonas aeruginosa is a versatile Gram-negative pathogen with intricate intracellular regulatory networks that enable it to adapt to and flourish in a variety of biotic and abiotic habitats. However, the mechanism permitting the persistent survival of P. aeruginosa within host tissues and causing chronic symptoms still remains largely elusive. By using in situ RNA sequencing, here we show that P. aeruginosa adopts different metabolic pathways and virulence repertoires to dominate the progression of acute and chronic lung infections. Notably, a virulence factor named TesG, which is controlled by the vital quorum-sensing system and secreted by the downstream type I secretion system, can suppress the host inflammatory response and facilitate the development of chronic lung infection. Mechanically, TesG can enter the intracellular compartment of macrophages through clathrin-mediated endocytosis, competitively inhibit the activity of eukaryotic small GTPase and thus suppress subsequent neutrophil influx, cell cytoskeletal rearrangement of macrophages and the secretion of cytokines and chemokines. Therefore, the identification of TesG in this study reveals a type I secretion apparatus of P. aeruginosa that functions during the host-pathogen interaction, and may open an avenue for the further mechanistic study of chronic respiratory diseases and the development of antibacterial therapy.
铜绿假单胞菌是一种多功能的革兰氏阴性病原体，具有复杂的细胞内调控网络，使其能够适应和繁荣于各种生物和非生物栖息地。然而，允许铜绿假单胞菌在宿主组织内持续生存并导致慢性症状的机制仍然很大程度上难以捉摸。通过使用原位 RNA 测序，我们在这里表明，铜绿假单胞菌采用不同的代谢途径和毒力库来主导急性和慢性肺部感染的进展。值得注意的是，一种名为 TesG 的毒力因子，受关键群体感应系统控制，并由下游 I 型分泌系统分泌，可抑制宿主炎症反应并促进慢性肺部感染的发展。在机制上，TesG 可以通过网格蛋白介导的内吞作用进入巨噬细胞的细胞内区室，竞争性抑制真核小 GTPase 的活性，从而抑制随后的中性粒细胞内流、巨噬细胞细胞骨架重排以及细胞因子和趋化因子的分泌。因此，本研究中 TesG 的鉴定揭示了铜绿假单胞菌在宿主-病原体相互作用过程中发挥作用的 I 型分泌装置，这可能为进一步研究慢性呼吸道疾病和抗菌治疗的发展开辟了新途径。
