Dissecting Virulence: Systematic and Functional Analyses of a Pathogenicity Island

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 101; no. 10; pp. 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: Journal Article
• Language: English
• Published: United States National Academy of Sciences 09-03-2004; National Acad Sciences
• 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
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.0400326101

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.