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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.

Miller CB, Pierlé SA, Brayton KA, Ochoa JN, Shah DH, Lahmers KK - Pathogens (2014)

Bottom Line: 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.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, WA 99164, USA.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus

Number of genes more highly transcribed in direct comparison between the UK-1 dam mutant (yellow oval) and UK-1 wt parent strain (blue oval) in (a) High Salt Luria Burtani (HSLB) and (b) low phosphate and magnesium concentration (LPM) media. Genes with a 2-fold or higher cut off and a p < 0.05 were selected. The numbers in common in the Venn diagram represent genes transcript levels not significantly different between UK-1 dam mutant and UK-1.
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Figure 1: Number of genes more highly transcribed in direct comparison between the UK-1 dam mutant (yellow oval) and UK-1 wt parent strain (blue oval) in (a) High Salt Luria Burtani (HSLB) and (b) low phosphate and magnesium concentration (LPM) media. Genes with a 2-fold or higher cut off and a p < 0.05 were selected. The numbers in common in the Venn diagram represent genes transcript levels not significantly different between UK-1 dam mutant and UK-1.

Mentions: Whole genome transcriptional activity in the UK-1 dam mutant and UK-1, its isogenic wt parent strain, were compared after growth in HSLB and LPM medium to identify differentially transcribed genes. Irrespective of the culture conditions used, the majority of the genes, 85% in HSLB and 91% in LPM, did not show significant transcriptional differences between the UK-1 dam mutant and the wt parent strain (Figure 1 and Supplementary Table 1). In the UK-1 dam mutant, 333 genes were identified with greater than 2-fold change and p < 0.05 in comparison to the wt parent strain when grown in HSLB. A similar comparison in the wt parent strain identified 272 genes in comparison to the UK-1 dam mutant (Figure 1a). When grown in LPM medium, 317 genes were highly transcribed in the UK-1 dam mutant whereas only 82 genes were highly transcribed in the wt parent strain (Figure 1b). In both culture conditions the UK-1 dam mutant transcribed genes more highly than the wt parent strain: 18% more genes in HSLB medium and 74% more genes in LPM medium. The proportion of highly transcribed genes was significantly different between the UK-1 dam mutant and the wt parent strain in both culture conditions (Fisher’s Exact test, p-value < 0.0001). The increased relative transcription observed in the UK-1 dam mutant in both culture conditions in comparison to the wt parent strain indicates that de-repression is consistent across different host-like microenvironments.


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.

Miller CB, Pierlé SA, Brayton KA, Ochoa JN, Shah DH, Lahmers KK - Pathogens (2014)

Number of genes more highly transcribed in direct comparison between the UK-1 dam mutant (yellow oval) and UK-1 wt parent strain (blue oval) in (a) High Salt Luria Burtani (HSLB) and (b) low phosphate and magnesium concentration (LPM) media. Genes with a 2-fold or higher cut off and a p < 0.05 were selected. The numbers in common in the Venn diagram represent genes transcript levels not significantly different between UK-1 dam mutant and UK-1.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4213855&req=5

Figure 1: Number of genes more highly transcribed in direct comparison between the UK-1 dam mutant (yellow oval) and UK-1 wt parent strain (blue oval) in (a) High Salt Luria Burtani (HSLB) and (b) low phosphate and magnesium concentration (LPM) media. Genes with a 2-fold or higher cut off and a p < 0.05 were selected. The numbers in common in the Venn diagram represent genes transcript levels not significantly different between UK-1 dam mutant and UK-1.
Mentions: Whole genome transcriptional activity in the UK-1 dam mutant and UK-1, its isogenic wt parent strain, were compared after growth in HSLB and LPM medium to identify differentially transcribed genes. Irrespective of the culture conditions used, the majority of the genes, 85% in HSLB and 91% in LPM, did not show significant transcriptional differences between the UK-1 dam mutant and the wt parent strain (Figure 1 and Supplementary Table 1). In the UK-1 dam mutant, 333 genes were identified with greater than 2-fold change and p < 0.05 in comparison to the wt parent strain when grown in HSLB. A similar comparison in the wt parent strain identified 272 genes in comparison to the UK-1 dam mutant (Figure 1a). When grown in LPM medium, 317 genes were highly transcribed in the UK-1 dam mutant whereas only 82 genes were highly transcribed in the wt parent strain (Figure 1b). In both culture conditions the UK-1 dam mutant transcribed genes more highly than the wt parent strain: 18% more genes in HSLB medium and 74% more genes in LPM medium. The proportion of highly transcribed genes was significantly different between the UK-1 dam mutant and the wt parent strain in both culture conditions (Fisher’s Exact test, p-value < 0.0001). The increased relative transcription observed in the UK-1 dam mutant in both culture conditions in comparison to the wt parent strain indicates that de-repression is consistent across different host-like microenvironments.

Bottom Line: 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.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, WA 99164, USA.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus