Abstract
Salmonella enterica serovar Typhimurium is arguably one of the most studied bacterial pathogens and successful infection requires the delivery of its virulence factors (effectors) directly into host cells via the type III secretion systems (T3SSs). Central to Salmonella pathogenesis, these effector proteins have been subjected to extensive studies over the years. Nevertheless, whether additional effectors exist remains unclear. Here we report the identification of a novel Salmonella T3SS effector STM1239 (which we renamed SopF) via quantitative secretome profiling. Immunoblotting and β-lactamase reporter assays confirmed the secretion and translocation of SopF in a T3SS-dependent manner. Moreover, ectopic expression of SopF caused significant toxicity in yeast cells. Importantly, genetic ablation of sopF led to Salmonella strains defective in intracellular replication within macrophages and the mutant were also markedly attenuated in a mouse model of infection. Our study underscores the use of quantitative secretome profiling in identifying novel virulence factors for bacterial pathogens.
Highlights
Salmonella enterica serovars are intracellular bacterial pathogens that can cause a wide spectrum of diseases, ranging from intestinal inflammation to life-threatening typhoid fever as a systemic infection
Typhimurium Secretome Identified a Putative T3SS Effector—Salmonella Typhimurium is arguably one of the best characterized models for bacterial pathogens and many of its T3SS effectors have been uncovered over the years by various approaches
A comprehensive catalogue of SPI-1 T3SS effectors has been lacking, which hampers a full understanding of SPI-1 functions
Summary
Salmonella enterica serovars are intracellular bacterial pathogens that can cause a wide spectrum of diseases, ranging from intestinal inflammation to life-threatening typhoid fever as a systemic infection. Similar strategies of secretome profiling by using quantitative proteomics have been successfully applied to further expand the effector repertoire of other bacterial pathogens including enteropathogenic Escherichia coli induced dissociation; ORF, open reading frame; MOI, multiplicity of infection; TCA, tricarboxylic acid; DMEM, Dulbecco’s Modified Eagle Medium; FBS, fetal bovine serum; PVDF, polyvinylidene difluoride; CI, competitive index; EPEC, enteropathogenic Escherichia coli; FDR, false discovery rate; HRP, horseradish peroxidase; HBSS, Hanks’ balanced salt solution; PGK, 3-phosphoglycerate kinase. Despite such significant progresses, a proteomic catalog of S. Our work highlights the use of quantitative secretome profiling in identifying novel bacterial virulence factors
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