Antigen selection based on expression levels during infection facilitates vaccine development for an intracellular pathogen

Rollenhagen, Claudia; Sörensen, Meike; Rizos, Konstantin; Hurvitz, Robert; Bumann, Dirk

doi:10.1073/pnas.0401283101

Cited by 90 publications

(90 citation statements)

References 47 publications

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“…Our data show that SseB immunization is protective in murine infection, reducing bacterial loads and increasing survival time after infection, which confirms and extends a previous report (63). It is not yet clear why a protein encoded by Salmonella pathogenicity island 2 would be recognized by antibody responses because these proteins would be expected to remain contained within infected cells.…”

Section: Discussionsupporting

confidence: 90%

Identification of a common immune signature in murine and human systemic Salmonellosis

Lee¹,

Liang

Juárez

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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Despite the importance of Salmonella infections in human and animal health, the target antigens of Salmonella -specific immunity remain poorly defined. We have previously shown evidence for antibody-mediating protection against invasive Salmonellosis in mice and African children. To generate an overview of antibody targeting in systemic Salmonellosis, a Salmonella proteomic array containing over 2,700 proteins was constructed and probed with immune sera from Salmonella -infected mice and humans. Analysis of multiple inbred mouse strains identified 117 antigens recognized by systemic antibody responses in murine Salmonellosis. Importantly, many of these antigens were independently identified as target antigens using sera from Malawian children with Salmonella bacteremia, validating the study of the murine model. Furthermore, vaccination with SseB, the most prominent antigenic target in Malawian children, provided mice with significant protection against Salmonella infection. Together, these data uncover an overlapping immune signature of disseminated Salmonellosis in mice and humans and provide a foundation for the generation of a protective subunit vaccine.

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Section: Discussionsupporting

confidence: 90%

Identification of a common immune signature in murine and human systemic Salmonellosis

Lee¹,

Liang

Juárez

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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“…S. Typhimurium s E also plays an important role in resistance to non-oxidative mammalian host defence mechanisms such as antimicrobial peptides (Humphreys et al, 1999;Crouch et al, 2005). Moreover, the S. Typhimurium rpoE gene has been shown to be up-regulated in S. Typhimurium within macrophages in vitro and murine tissues in vivo (Eriksson et al, 2003;Rollenhagen et al, 2004). These results indicate that the genes of the s E regulon should play roles in all these processes.…”

Section: The Activity Of Smentioning

confidence: 99%

Identification of the σ E regulon of Salmonella enterica serovar Typhimurium

et al. 2006

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The extracytoplasmic function sigma factor, s E , has been shown to play a critical role in virulence of Salmonella enterica serovar Typhimurium (S. Typhimurium). The previously optimized two-plasmid system has been used to identify S. Typhimurium promoters recognized by RNA polymerase containing s E . This method allowed identification of 34 s E -dependent promoters that direct expression of 62 genes in S. Typhimurium, 23 of which (including several specific for S. Typhimurium) have not been identified previously to be dependent upon s E in Escherichia coli. The promoters were confirmed in S. Typhimurium and transcriptional start points of the promoters were determined by S1-nuclease mapping. All the promoters contained sequences highly similar to the consensus sequence of s E -dependent promoters. The identified genes belonging to the S.Typhimurium s E -regulon encode proteins involved in primary metabolism, DNA repair systems and outer-membrane biogenesis, and regulatory proteins, periplasmic proteases and folding factors, proposed lipoproteins, and inner-and outer-membrane proteins with unknown functions. Several of these s E -dependent genes have been shown to play a role in virulence of S. Typhimurium.

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“…The knowledge gathered by IVET and DFI about the genes that are required for establishment of a pathogen in its host environment can be exploited for identifying new targets to direct new antimicrobial drug development or the construction of live attenuated vaccines (4,235,252). The subset of bacterial antigens that are highly expressed during infection can be rapidly evaluated for use in vaccine development (229). Hemolysin A and listeriolysin, for instance, are IVET-isolated genes which are highly suitable for the elicitation of cell-mediated immunity and might be used as tools for vaccine delivery (50).…”

Section: Ivet: a Powerful And Flexible Toolmentioning

confidence: 99%

Unraveling the Secret Lives of Bacteria: Use of In Vivo Expression Technology and Differential Fluorescence Induction Promoter Traps as Tools for Exploring Niche-Specific Gene Expression

Rediers

Rainey

Vanderleyden

et al. 2005

Microbiol Mol Biol Rev

139

120

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A major challenge for microbiologists is to elucidate the strategies deployed by microorganisms to adapt to and thrive in highly complex and dynamic environments. In vitro studies, including those monitoring genomewide changes, have proven their value, but they can, at best, mimic only a subset of the ensemble of abiotic and biotic stimuli that microorganisms experience in their natural habitats. The widely used gene-to-phenotype approach involves the identification of altered niche-related phenotypes on the basis of gene inactivation. However, many traits contributing to ecological performance that, upon inactivation, result in only subtle or difficult to score phenotypic changes are likely to be overlooked by this otherwise powerful approach. Based on the premise that many, if not most, of the corresponding genes will be induced or upregulated in the environment under study, ecologically significant genes can alternatively be traced using the promoter trap techniques differential fluorescence induction and in vivo expression technology (IVET). The potential and limitations are discussed for the different IVET selection strategies and system-specific variants thereof. Based on a compendium of genes that have emerged from these promoter-trapping studies, several functional groups have been distinguished, and their physiological relevance is illustrated with follow-up studies of selected genes. In addition to confirming results from largely complementary approaches such as signature-tagged mutagenesis, some unexpected parallels as well as distinguishing features of microbial phenotypic acclimation in diverse environmental niches have surfaced. On the other hand, by the identification of a large proportion of genes with unknown function, these promoter-trapping studies underscore how little we know about the secret lives of bacteria and other microorganisms

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Antigen selection based on expression levels during infection facilitates vaccine development for an intracellular pathogen

Cited by 90 publications

References 47 publications

Identification of a common immune signature in murine and human systemic Salmonellosis

Identification of a common immune signature in murine and human systemic Salmonellosis

Identification of the σ E regulon of Salmonella enterica serovar Typhimurium

Unraveling the Secret Lives of Bacteria: Use of In Vivo Expression Technology and Differential Fluorescence Induction Promoter Traps as Tools for Exploring Niche-Specific Gene Expression

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