The type III secretion system facilitates systemic infections of Pseudomonas aeruginosa in the clinic

作者：Tiantian Wu, Zhenchuan Zhang, Tong Li, Xu Dong, Dan Wu, Lixia Zhu, Kaijin Xu, Ying Zhang · 发表于：Microbiology Spectrum · 年份：2023 · DOI：10.1128/spectrum.02224-23 · 被引用次数：15 · 研究领域：Antibiotic Resistance in Bacteria、Vibrio bacteria research studies、Bacterial biofilms and quorum sensing

ABSTRACT Pseudomonas aeruginosa is a major opportunistic pathogen that can cause severe systemic infections. Here, we found that the type III secretion system effector ExoU was the main determinant of pathogenicity of a highly virulent clinical isolate strain, BSI_S5, of P. aeruginosa , which caused severe bloodstream infections and belongs to ST463/O4. Deletion of exoU showed significantly attenuated cytotoxicity and virulence in vivo , while deletion of two other unique genes from strain BSI_S5, chr_1696 and chr_4238 , which encodes type I secretion system permease/ATPase or polysaccharide biosynthesis protein, respectively, caused no apparent loss of toxicity compared to the parent strain, and complementation of the ΔexoU mutant restored its virulence. The presence of ExoU-induced lung lesions and the mucosal damage of gallbladder in mice, and the replication of the ΔexoU mutant was hindered in vivo compared with the parent strain. We show here for the first time that a clinical isolate with intact exoU harbored a mutation of T→G substitution in the adjacent specific Pseudomonas chaperone for ExoU ( spcU ), which caused phenylalanine to valine change at amino acid 94 of SpcU, resulting in significant loss of cytotoxicity. This finding suggests that intact exoU is not sufficient for cytotoxicity, but a functional downstream SpcU is required for ExoU secretion and cytotoxicity. Finally, we found that BSI_S5 harbored two types of insertion sequences adjacent to exoU , suggest...