Deletion of Salmonella pathogenicity islands SPI-1, 2 and 3 induces substantial morphological and metabolic alternation and protective immune potential

文献类型： 外文期刊

第一作者： Liu, Gaosong

作者： Liu, Gaosong;Lu, Xuelian;Tian, Qiufeng;Zhang, Wanjiang;Yi, Fei;Zhang, Yueling;Yu, Shenye

作者机构：

关键词： Salmonella pathogenicity islands (SPIs); morphology; carbon source metabolism; pathogenicity; immunogenicity; live attenuated vaccine

期刊名称：JOURNAL OF INTEGRATIVE AGRICULTURE （ 影响因子：4.4； 五年影响因子：4.8 ）

ISSN： 2095-3119

年卷期： 2025 年 24 卷 1 期

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收录情况： SCI

摘要： The Salmonella pathogenicity islands (SPIs) play crucial roles in the progression of Salmonella infection. In this study, we constructed an improved lambda Red homologous recombination system to prepare single and triple deletion mutants of 3 prominent SPIs (SPI-1, 2, and 3), aiming at the impact of deletion on morphology, carbon source metabolism, adhesion and invasion capacity, in vivo colonization, and immune efficacy in chicks. Our examination revealed that the surface of the single deletion mutants (SM6 Delta SPI1, Delta SPI2, and Delta SPI3) exhibited a more rugged texture and appeared to be enveloped in a layer of transparent colloid, whereas the morphology of the triple deletion mutant (SM6 Delta SPI1&2&3) remained unaltered when compared to the parent strain. The carbon metabolic spectrum of the SPI mutants underwent profound alterations, with a notable and statistically significant modification observed in 30 out of 95 carbon sources, primarily carbohydrates (17 out of 30). Furthermore, the adhesion capacity of the 4 mutants to Caco-2 cells was significantly reduced when compared to that of the parent strain. Moreover, the invasion capacity of mutants SM6 Delta SPI1 and SM6 Delta SPI1&2&3 exhibited a substantial decrease, while it was enhanced to varying degrees for SM6 Delta SPI3 and SM6 Delta SPI2. Importantly, none of the 4 mutants induced any clinical symptoms in the chicks. However, they did transiently colonize the spleen and liver. Notably, the SM6 Delta SPI1&2&3 mutant was rapidly cleared from both the spleen and liver within 8 days post-infection and no notable pathological changes were observed in the organs. Additionally, when challenged, the mutants immunized groups displayed a significant increase in antibody levels and alterations in the CD3+CD4+and CD3+CD8+ subpopulations, and the levels of IL-4 and IFN-gamma cytokines in the SM6 Delta SPI1&2&3 immunized chicken serum surpassed those of other groups. In summary, the successful construction of the 4 SPI mutants lays the groundwork for further exploration into the pathogenic (including metabolic) mechanisms of SPIs and the development of safe and effective live attenuated Salmonella vaccines or carriers.

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