在目前的研究中,两株鼠伤寒沙门氏菌,JOL912和JOL1800是通过lon和cpxR基因的框内缺失从野生型JOL401菌株进行工程改造的,JOL1800也缺少rfaL。这些缺失显著减弱了菌株,损害他们的细胞内生存和创造独特的免疫学谱。本研究调查了这些菌株对体内常见的各种非生物胁迫条件的反应,包括温度,酸度,渗透,和氧化应激。值得注意的是,与其他应激源相比,冷应激导致沙门氏菌入侵增加的趋势不显着。尽管观察到了衰减,进入机制没有显著改变(触发器与在这些菌株之间注意到拉链),尽管差异明显取决于宿主细胞类型。两种菌株都有效地定位在细胞质内,展示了它们侵入细胞内环境并与之相互作用的能力。免疫学,JOL912引起了强烈的反应,以核因子κB(NF-kB)的大量激活为标志,和趋化因子,白细胞介素8(CXCL8)和白细胞介素10(CXCL10),与野生型JOL401相当(与JOL1800相比增加了四倍)。相比之下,JOL1800表现出最小的免疫应答。此外,这些减弱影响了细胞周期蛋白D1和B1以及胱天蛋白酶3和7的表达,表明细胞周期停滞在G2/M期,并促进了G0/G1向S期的转变,伴随着受感染细胞的凋亡。这些发现为管理协会的机制提供了有价值的见解,内化,和沙门氏菌突变体的存活,增强我们对它们对宿主细胞生理学的调节作用的理解。
In the current study, two Salmonella Typhimurium strains, JOL 912 and JOL 1800, were engineered from the wild-type JOL 401 strain through in-frame deletions of the lon and cpxR genes, with JOL 1800 also lacking rfaL. These deletions significantly attenuated the strains, impairing their intracellular survival and creating unique immunological profiles. This study investigates the response of these strains to various abiotic stress conditions commonly experienced in vivo, including temperature, acidity, osmotic, and oxidative stress. Notably, cold stress induced a non-significant trend towards increased invasion by Salmonella compared to other stressors. Despite the observed attenuation, no significant alterations in entry mechanisms (trigger vs. zipper) were noted between these strains, although variations were evident depending on the host cell type. Both strains effectively localized within the cytoplasm, demonstrating their ability to invade and interact with the intracellular environment. Immunologically, JOL 912 elicited a robust response, marked by substantial activation of nuclear factor kappa B (NF-kB), and chemokines, interleukin 8 (CXCL 8) and interleukin 10 (CXCL 10), comparable to the wild-type JOL 401 (over a fourfold increase compared to JOL 1800). In contrast, JOL 1800 exhibited a minimal immune response. Additionally, these attenuations influenced the expression of cyclins D1 and B1 and caspases 3 and 7, indicating cell cycle arrest at the G2/M phase and promotion of the G0/G1 to S phase transition, alongside apoptosis in infected cells. These findings provide valuable insights into the mechanisms governing the association, internalization, and survival of Salmonella mutants, enhancing our understanding of their regulatory effects on host cell physiology.