Dissecting Virulence: Systematic and Functional Analyses of a Pathogenicity Island

Bacterial pathogenicity islands (PAI) often encode both effector molecules responsible for disease and secretion systems that deliver these effectors to host cells. Human enterohemorrhagic Escherichia coli (EHEC), enteropathogenic E. coli, and the mouse pathogen Citrobacter rodentium (CR) possess th...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2004-03, Vol.101 (10), p.3597-3602
Main Authors: Deng, Wanyin, Puente, José L., Gruenheid, Samantha, Li, Yuling, Vallance, Bruce A., Vázquez, Alejandra, Barba, Jeannette, Ibarra, J. Antonio, O'Donnell, Paul, Metalnikov, Pavel, Ashman, Keith, Lee, Sansan, Goode, David, Pawson, Tony, Finlay, B. Brett, Falkow, Stanley
Format: Article
Language:English
Subjects:
Animals
Bacteria
Biological Sciences
Citrobacter rodentium
Citrobacter rodentium - genetics
Citrobacter rodentium - pathogenicity
Disease
Enterobacteriaceae Infections - etiology
Enterobacteriaceae Infections - microbiology
Escherichia coli
Escherichia coli - genetics
Escherichia coli - pathogenicity
Gene expression regulation
Gene Expression Regulation, Bacterial
Genes
Genes, Bacterial
Genomes
Genomic Islands
Humans
Mice
Mice, Inbred C3H
Mice, Inbred C57BL
Microbiology
Mutation
pathogenicity islands
Pathogens
Plasmids
Regulator genes
Secretion
Transcriptional regulatory elements
Virulence
Virulence - genetics
Virulence factors
Virulence Factors - genetics
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Summary:Bacterial pathogenicity islands (PAI) often encode both effector molecules responsible for disease and secretion systems that deliver these effectors to host cells. Human enterohemorrhagic Escherichia coli (EHEC), enteropathogenic E. coli, and the mouse pathogen Citrobacter rodentium (CR) possess the locus of enterocyte effacement (LEE) PAI. We systematically mutagenized all 41 CR LEE genes and functionally characterized these mutants in vitro and in a murine infection model. We identified 33 virulence factors, including two virulence regulators and a hierarchical switch for type III secretion. In addition, 7 potential type III effectors encoded outside the LEE were identified by using a proteomics approach. These non-LEE effectors are encoded by three uncharacterized PAIs in EHEC O157, suggesting that these PAIs act cooperatively with the LEE in pathogenesis. Our findings provide significant insights into bacterial virulence mechanisms and disease.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0400326101