关键词: PagN Salmonella evasion host cell vacuole hyper-replication outer membrane protein

Mesh : Salmonella typhimurium / genetics pathogenicity Cytosol / microbiology Vacuoles / microbiology metabolism Bacterial Proteins / genetics metabolism Virulence Factors / genetics metabolism Humans Virulence Salmonella Infections / microbiology HeLa Cells Epithelial Cells / microbiology Gene Expression Regulation, Bacterial

来  源:   DOI:10.1080/21505594.2024.2357670   PDF(Pubmed)

Abstract:
Salmonella enterica subspecies enterica serovar Typhimurium is an intracellular pathogen that invades and colonizes the intestinal epithelium. Following bacterial invasion, Salmonella is enclosed within a membrane-bound vacuole known as a Salmonella-containing vacuole (SCV). However, a subset of Salmonella has the capability to prematurely rupture the SCV and escape, resulting in Salmonella hyper-replication within the cytosol of epithelial cells. A recently published RNA-seq study provides an overview of cytosolic and vacuolar upregulated genes and highlights pagN vacuolar upregulation. Here, using transcription kinetics, protein production profile, and immunofluorescence microscopy, we showed that PagN is exclusively produced by Salmonella in SCV. Gentamicin protection and chloroquine resistance assays were performed to demonstrate that deletion of pagN affects Salmonella replication by affecting the cytosolic bacterial population. This study presents the first example of a Salmonella virulence factor expressed within the endocytic compartment, which has a significant impact on the dynamics of Salmonella cytosolic hyper-replication.
摘要:
肠沙门氏菌亚种肠血清型鼠伤寒沙门氏菌是一种细胞内病原体,侵入并定居肠上皮。细菌入侵后,沙门氏菌被封闭在称为含沙门氏菌的液泡(SCV)的膜结合液泡中。然而,沙门氏菌的一个子集有能力过早地使SCV破裂并逃脱,导致沙门氏菌在上皮细胞的胞质溶胶内过度复制。最近发表的RNA-seq研究提供了胞浆和液泡上调基因的概述,并强调了pagN液泡上调。这里,使用转录动力学,蛋白质生产概况,和免疫荧光显微镜,我们表明PagN是由SCV中的沙门氏菌独家产生的。进行了庆大霉素保护和氯喹抗性测定,以证明pagN的缺失通过影响胞质细菌种群来影响沙门氏菌的复制。这项研究提出了沙门氏菌毒力因子在内吞室表达的第一个例子,这对沙门氏菌胞浆过度复制的动力学有显著影响。
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