Overexpression of T3SS translocation signals in Salmonella causes delayed attenuation.
Overexpression of T3SS translocation signals in Salmonella causes delayed attenuation.
复制标题
沙门氏菌中 T3SS 易位信号的过度表达会导致延迟衰减。
DOI：
10.1128/iai.00329-23
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发表时间：
2024
影响因子：
3.1
通讯作者：
Miao,EdwardA
中科院分区：
文献类型：
--
作者：
Abele,TaylorJ;Billman,ZacharyP;Harvest,CarissaK;Bryan,AlexiaK;Larson,HeatherN;Coers,Jörn;Miao,EdwardA
工程病原体是发现微生物致病机理和宿主防御的新细节的有用方法。然而，工程可能导致脱靶效应。我们以前engineeredSalmonella entericaserovar Typhimurium过表达分泌信号的3型分泌系统效应SspH 1融合域的其他蛋白质作为货物。这种工程在小鼠感染后的前48小时内对细菌没有毒力成本。在这里，我们表明，48小时后，工程菌表现出与SspH 1易位信号表达量相关的衰减。在IFN-γ缺陷型小鼠中，这种减毒作用减弱。相反，在预先存在感染的情况下，衰减加速。我们推测炎症信号改变了靶细胞的生理学方面，这使得宿主细胞对S的耐受性降低。鼠伤寒感染。这种增加的难度要求细菌以最高效率利用其T3 SS，这可以被工程效应物破坏。
Engineering pathogens is a useful method for discovering new details of microbial pathogenesis and host defense. However, engineering can result in off-target effects. We previously engineeredSalmonella entericaserovar Typhimurium to overexpress the secretion signal of the type 3 secretion system effector SspH1 fused with domains of other proteins as cargo. Such engineering had no virulence cost to the bacteria for the first 48 hours post infection in mice. Here, we show that after 48 hours, the engineered bacteria manifest an attenuation that correlates with the quantity of the SspH1 translocation signal expressed. In IFN-γ-deficient mice, this attenuation was weakened. Conversely, the attenuation was accelerated in the context of a pre-existing infection. We speculate that inflammatory signals change aspects of the target cell’s physiology, which makes host cells less permissive toS. Typhimurium infection. This increased degree of difficulty requires the bacteria to utilize its T3SS at peak efficiency, which can be disrupted by engineered effectors.