Transcriptional Profiling of a Cross-Protective serovar Typhimurium UK-1 Mutant Identifies a Set of Genes More Transcriptionally Active Compared to Wild-Type, and Stably Transcribed across Biologically Relevant Microenvironments.

Vaccination with serovar Typhimurium lacking DNA adenine methyltransferase confers cross-protective immunity against multiple 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 Typhimurium DNA adenine methyltransferase mutant strain (UK-1 mutant) derived from the parental UK-1 strain, and assessed the transcriptional profile of the UK-1 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 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 serovars. The strategy employed here helps to identify potentially conserved proteins produced by the UK-1 mutant that stimulate and/or modulate the development of cross-protective immune responses toward multiple serotypes.