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 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.
Biotechnology Laboratory, University of British Columbia, Vancouver, BC, Canada V6T 1Z3.
Wanyin
W
Deng
José L
JL
Puente
Samantha
S
Gruenheid
Yuling
Y
Li
Bruce A
BA
Vallance
Alejandra
A
Vázquez
Jeannette
J
Barba
J Antonio
JA
Ibarra
Paul
P
O'Donnell
Pavel
P
Metalnikov
Keith
K
Ashman
Sansan
S
Lee
David
D
Goode
Tony
T
Pawson
B Brett
BB
Finlay
D000818:Animals; D044082:Citrobacter rodentium / Q000235:genetics / Q000472:pathogenicity; D004756:Enterobacteriaceae Infections / Q000209:etiology / Q000382:microbiology; D004926:Escherichia coli / Q000235:genetics / Q000472:pathogenicity; D015964:Gene Expression Regulation, Bacterial; D005798:Genes, Bacterial; D044404:Genomic Islands; D006801:Humans; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D014774:Virulence / Q000235:genetics*; D037521:Virulence Factors / Q000235:genetics
D037521:Virulence Factors