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首页> 美国卫生研究院文献>Pathogens >Transcriptional Profiling of a Cross-Protective Salmonella enterica serovar Typhimurium UK-1 dam Mutant Identifies a Set of Genes More Transcriptionally Active Compared to Wild-Type and Stably Transcribed across Biologically Relevant Microenvironments
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Transcriptional Profiling of a Cross-Protective Salmonella enterica serovar Typhimurium UK-1 dam Mutant Identifies a Set of Genes More Transcriptionally Active Compared to Wild-Type and Stably Transcribed across Biologically Relevant Microenvironments

机译：跨保护肠炎沙门氏菌血清型鼠伤寒UK-1大坝突变体的转录谱分析鉴定了一组与野生型相比转录活性更高的基因并且在生物学相关的微环境中稳定转录。

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Vaccination with Salmonella enterica serovar Typhimurium lacking DNA adenine methyltransferase confers cross-protective immunity against multiple Salmonella serotypes. The mechanistic basis is thought to be associated with the de-repression of genes that are tightly regulated when transiting from one microenvironment to another. This de-repression provides a potential means for the production of a more highly expressed and stable antigenic repertoire capable of inducing cross-protective immune responses. To identify genes encoding proteins that may contribute to cross-protective immunity, we used a Salmonella Typhimurium DNA adenine methyltransferase mutant strain (UK-1 dam mutant) derived from the parental UK-1 strain, and assessed the transcriptional profile of the UK-1 dam mutant and UK-1 strain grown under conditions that simulate the intestinal or endosomal microenvironments encountered during the infective process. As expected, the transcriptional profile of the UK-1 dam mutant identified a set of genes more transcriptionally active when compared directly to UK-1, and stably transcribed in biologically relevant culture conditions. Further, 22% of these genes were more highly transcribed in comparison to two other clinically-relevant Salmonella serovars. The strategy employed here helps to identify potentially conserved proteins produced by the UK-1 dam mutant that stimulate and/or modulate the development of cross-protective immune responses toward multiple Salmonella serotypes.
机译：缺乏DNA腺嘌呤甲基转移酶的肠炎沙门氏菌血清型鼠伤寒疫苗接种可赋予针对多种沙门氏菌血清型的交叉保护性免疫力。机理的基础被认为与从一个微环境过渡到另一个微环境时受到严格调节的基因的抑制相关。这种抑制作用提供了一种潜在的手段，用于产生能够诱导交叉保护性免疫应答的更高表达和稳定的抗原库。为了鉴定编码可能有助于交叉保护性免疫的蛋白质的基因，我们使用了源自亲本UK-1株的鼠伤寒沙门氏菌DNA腺嘌呤甲基转移酶突变株（UK-1 dam突变株），并评估了UK-1的转录谱dam突变体和UK-1菌株在模拟感染过程中遇到的肠道或内体微环境的条件下生长。不出所料，UK-1 dam突变体的转录谱鉴定出了与UK-1直接相比更具转录活性的一组基因，并在生物学相关的培养条件下稳定转录。此外，与另外两个与临床相关的沙门氏菌血清型相比，这些基因中有22％的转录程度更高。本文采用的策略有助于鉴定UK-1大坝突变体产生的潜在保守蛋白，该蛋白刺激和/或调节针对多种沙门氏菌血清型的交叉保护性免疫应答的发展。

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