Negative Regulation of Salmonella Pathogenicity Island 2 Is Required for Contextual Control of Virulence during Typhoid

Salmonella enterica relies on a type III secretion system encoded in Salmonella pathogenicity island-2 (SPI-2) to survive and replicate within macrophages at systemic sites during typhoid. SPI-2 virulence is induced upon entry into macrophages, but the mechanisms of SPI-2 gene control in vivo remain...

Full description

Saved in:
Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2005-11, Vol.102 (48), p.17460-17465
Main Authors: Brian K. Coombes, Wickham, Mark E., Michael J. Lowden, Brown, Nat F., Finlay, B. Brett, Curtiss, Roy
Format: Article
Language:English
Subjects:
Animals
Bacteria
Bacterial Proteins - metabolism
Biological Sciences
Cell Line
DNA-Binding Proteins - genetics
DNA-Binding Proteins - metabolism
Gene expression
Gene Expression Profiling
Gene Expression Regulation, Bacterial - genetics
Genes
HeLa Cells
Humans
Infections
Liver
Membrane Proteins - metabolism
Mice
Microbiology
Mutation
Pathogens
Phenotypes
Reverse Transcriptase Polymerase Chain Reaction
Salmonella
Salmonella enterica
Salmonella typhi - metabolism
Salmonella typhi - pathogenicity
Spleen
Transcriptional regulatory elements
Typhoid
Typhoid Fever - metabolism
Virulence
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Salmonella enterica relies on a type III secretion system encoded in Salmonella pathogenicity island-2 (SPI-2) to survive and replicate within macrophages at systemic sites during typhoid. SPI-2 virulence is induced upon entry into macrophages, but the mechanisms of SPI-2 gene control in vivo remain unclear, particularly with regard to negative regulators that control the contextual activation of SPI-2. Here, we identified and characterized YdgT as a negative modulator of the SPI-2 pathogenicity island and established that this negative regulation is central to systemic patho-genesis because ydgT mutants overexpressing typhoid virulence genes were ultimately attenuated during infection. ydgT mutants displayed a biphasic virulence phenotype during in vivo competitive infections that consisted of an early "gain-of-virulence" dependent on SPI-2 activation, followed by attenuation later in infection indicating that proper contextual regulation of SPI-2 by YdgT is necessary for full virulence during systemic colonization. These data suggest that overexpression of virulence-associated type III secretion genes can have an adverse effect on bacterial pathogenesis in vivo.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0505401102