Induction and evasion of host defenses by type 1-piliated uropathogenic Escherichia coli.
Virtually all uropathogenic strains of Escherichia coli encode filamentous surface adhesive organelles called type 1 pili. High-resolution electron microscopy of infected mouse bladders revealed that type 1 pilus tips interacted directly with the lumenal surface of the bladder, which is embedded with hexagonal arrays of integral membrane glycoproteins known as uroplakins. Attached pili were shortened and facilitated intimate contact of the bacteria with the uroplakin-coated host cells. Bacterial attachment resulted in exfoliation of host bladder epithelial cells as part of an innate host defense system. Exfoliation occurred through a rapid apoptosis-like mechanism involving caspase activation and host DNA fragmentation. Bacteria resisted clearance in the face of host defenses within the bladder by invading into the epithelium.
Mulvey
M A
MA
Department of Molecular Microbiology and Microbial Pathogenesis, Box 8230, Washington University School of Medicine, 660 S. Euclid Avenue, St. Louis, MO 63110, USA.
Lopez-Boado
Y S
YS
Wilson
C L
CL
Roth
R
R
Parks
W C
WC
Heuser
J
J
Hultgren
S J
SJ
D018829:Adhesins, Bacterial / Q000378:metabolism; D018830:Adhesins, Escherichia coli; D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis; D001422:Bacterial Adhesion; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D003556:Cystitis / Q000382:microbiology* / Q000473:pathology; D053938:DNA Fragmentation; D004926:Escherichia coli / Q000235:genetics / Q000472:pathogenicity*; D004927:Escherichia coli Infections / Q000382:microbiology* / Q000473:pathology; D005260:Female; D036781:Fimbriae Proteins; D010861:Fimbriae, Bacterial / Q000502:physiology / Q000648:ultrastructure; D020287:In Situ Nick-End Labeling; D008562:Membrane Glycoproteins / Q000032:analysis / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008854:Microscopy, Electron; D008855:Microscopy, Electron, Scanning; D059470:Tetraspanins; D001743:Urinary Bladder / Q000737:chemistry / Q000382:microbiology* / Q000473:pathology; D060167:Uroplakin Ia; D060169:Uroplakin Ib; D019459:Urothelium / Q000382:microbiology / Q000473:pathology
D018829:Adhesins, Bacterial; D018830:Adhesins, Escherichia coli; D000590:Amino Acid Chloromethyl Ketones; D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors; D008562:Membrane Glycoproteins; D059470:Tetraspanins; C086452:UPK1B protein, human; C490123:Upk1a protein, mouse; C490124:Upk1b protein, mouse; D060167:Uroplakin Ia; D060169:Uroplakin Ib; C103192:butyloxycarbonyl-O-methyl-aspartyl-fluoromethyl ketone; C058769:fimH protein, E coli; D036781:Fimbriae Proteins; D020169:Caspases