TY - JOUR
T1 - Dissecting virulence
T2 - Systematic and functional analyses of a pathogenicity island
AU - Deng, Wanyin
AU - Puente, José L.
AU - Gruenheid, Samantha
AU - Li, Yuling
AU - Vallance, Bruce A.
AU - Vázquez, Alejandra
AU - Barba, Jeannette
AU - Ibarra, J. Antonio
AU - O'Donnell, Paul
AU - Metalnikov, Pavel
AU - Ashman, Keith
AU - Lee, Sansan
AU - Goode, David
AU - Pawson, Tony
AU - Finlay, B. Brett
PY - 2004/3/9
Y1 - 2004/3/9
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=12144289554&partnerID=8YFLogxK
U2 - 10.1073/pnas.0400326101
DO - 10.1073/pnas.0400326101
M3 - Artículo
C2 - 14988506
AN - SCOPUS:12144289554
SN - 0027-8424
VL - 101
SP - 3597
EP - 3602
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 10
ER -
