Dissecting virulence: Systematic and functional analyses of a pathogenicity island

Wanyin Deng, José L. Puente, Samantha Gruenheid, Yuling Li, Bruce A. Vallance, Alejandra Vázquez, Jeannette Barba, J. Antonio Ibarra, Paul O'Donnell, Pavel Metalnikov, Keith Ashman, Sansan Lee, David Goode, Tony Pawson, B. Brett Finlay

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Abstract

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.
Original languageAmerican English
Pages (from-to)3597-3602
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
DOIs
StatePublished - 9 Mar 2004
Externally publishedYes

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Deng, W., Puente, J. L., Gruenheid, S., Li, Y., Vallance, B. A., Vázquez, A., Barba, J., Ibarra, J. A., O'Donnell, P., Metalnikov, P., Ashman, K., Lee, S., Goode, D., Pawson, T., & Finlay, B. B. (2004). Dissecting virulence: Systematic and functional analyses of a pathogenicity island. Proceedings of the National Academy of Sciences of the United States of America, 3597-3602. https://doi.org/10.1073/pnas.0400326101