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

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....

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Bibliographic Details
Published in:Pathogens (Basel) 2014-05, Vol.3 (2), p.417-436
Main Authors: Miller, Claire B, Pierlé, Sebastian Aguilar, Brayton, Kelly A, Ochoa, Jennine N, Shah, Devendra H, Lahmers, Kevin K
Format: Article
Language:English
Subjects:
bacteriophage
Deoxyribonucleic acid
DNA
DNA adenine methyltransferase
fimbriae
Genes
Hypotheses
immunity
Infections
Livestock
Microenvironments
Mutants
Pathogens
Proteins
Salmonella
Salmonella enterica
Salmonella Typhimurium
transcriptome
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Summary: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.
ISSN:2076-0817
2076-0817
DOI:10.3390/pathogens3020417