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Science 25 April 1997:
Vol. 276. no. 5312, pp. 607 - 611
DOI: 10.1126/science.276.5312.607

Reports

Prevention of Mucosal Escherichia coli Infection by FimH-Adhesin-Based Systemic Vaccination

Solomon Langermann, * Susan Palaszynski, Michelle Barnhart, Gale Auguste, Jerome S. Pinkner, Jeanne Burlein, Philip Barren, Scott Koenig, Simon Leath, C. Hal Jones, Scott J. Hultgren *

Virtually all uropathogenic strains of Escherichia coli, the primary cause of cystitis, assemble adhesive surface organelles called type 1 pili that contain the FimH adhesin. Sera from animals vaccinated with candidate FimH vaccines inhibited uropathogenic E. coli from binding to human bladder cells in vitro. Immunization with FimH reduced in vivo colonization of the bladder mucosa by more than 99 percent in a murine cystitis model, and immunoglobulin G to FimH was detected in urinary samples from protected mice. Furthermore, passive systemic administration of immune sera to FimH also resulted in reduced bladder colonization by uropathogenic E. coli. This approach may represent a means of preventing recurrent and acute infections of the urogenital mucosa.

S. Langermann, S. Palaszynski, G. Auguste, J. Burlein, P. Barren, S. Koenig, S. Leath, MedImmune, Inc., Gaithersburg, MD 20878, USA.
M. Barnhart, J. S. Pinkner, C. Hal Jones, S. J. Hultgren, Department of Molecular Microbiology, Washington University, St. Louis, MO 63110, USA.
*   To whom correspondence should be addressed.


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Microbiology 145, 2683-2690
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Antigen-43-Mediated Autoaggregation of Escherichia coli Is Blocked by Fimbriation.
H. Hasman, T. Chakraborty, and P. Klemm (1999)
J. Bacteriol. 181, 4834-4841
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Requirement of MrpH for Mannose-Resistant Proteus-Like Fimbria-Mediated Hemagglutination by Proteus mirabilis.
X. Li, D. E. Johnson, and H. L. T. Mobley (1999)
Infect. Immun. 67, 2822-2833
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Increased Type 1 Fimbrial Expression among Commensal Escherichia coli Isolates in the Murine Cecum following Catabolic Stress.
B. A. Hendrickson, J. Guo, R. Laughlin, Y. Chen, and J. C. Alverdy (1999)
Infect. Immun. 67, 745-753
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Virulence Properties of Escherichia coli 83972, a Prototype Strain Associated with Asymptomatic Bacteriuria.
R. A. Hull, D. C. Rudy, W. H. Donovan, I. E. Wieser, C. Stewart, and R. O. Darouiche (1999)
Infect. Immun. 67, 429-432
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Induction and Evasion of Host Defenses by Type 1-Piliated Uropathogenic Escherichia coli.
M. A. Mulvey, Y. S. Lopez-Boado, C. L. Wilson, R. Roth, W. C. Parks, J. Heuser, and S. J. Hultgren (1998)
Science 282, 1494-1497
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Pathogenic adaptation of Escherichia coli by natural variation of the FimH adhesin.
E. V. Sokurenko, V. Chesnokova, D. E. Dykhuizen, I. Ofek, X.-R. Wu, K. A. Krogfelt, C. Struve, M. A. Schembri, and D. L. Hasty (1998)
PNAS 95, 8922-8926
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In Vivo Phase Variation of Escherichia coli Type 1 Fimbrial Genes in Women with Urinary Tract Infection.
J. K. Lim, N. W. Gunther IV, H. Zhao, D. E. Johnson, S. K. Keay, and H. L. T. Mobley (1998)
Infect. Immun. 66, 3303-3310
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Adherence of Streptococcus pneumoniae to Human Bronchial Epithelial Cells (BEAS-2B).
J. E. Adamou, T. M. Wizemann, P. Barren, and S. Langermann (1998)
Infect. Immun. 66, 820-822
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Helicobacter pylori Adhesin Binding Fucosylated Histo-Blood Group Antigens Revealed by Retagging.
D. Ilver, A. Arnqvist, J. Ögren, I. Frick, D. Kersulyte, E. T. Incecik, D. E. Berg, A. Covacci, L. Engstrand, and T. Borén (1998)
Science 279, 373-377
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A Vaccine Against UTIs?.
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Journal Watch Women's Health 1997, 23
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HOPE FOR A VACCINE AGAINST RECURRENT UTIs.
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Tamm-Horsfall Protein Binds to Type 1 Fimbriated Escherichia coli and Prevents E. coli from Binding to Uroplakin Ia and Ib Receptors.
J. Pak, Y. Pu, Z.-T. Zhang, D. L. Hasty, and X.-R. Wu (2001)
J. Biol. Chem. 276, 9924-9930
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Regulation of Matrilysin Expression in Airway Epithelial Cells by Pseudomonas aeruginosa Flagellin.
Y. S. Lopez-Boado, C. L. Wilson, and W. C. Parks (2001)
J. Biol. Chem. 276, 41417-41423
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From the Cover: PapD-like chaperones provide the missing information for folding of pilin proteins.
M. M. Barnhart, J. S. Pinkner, G. E. Soto, F. G. Sauer, S. Langermann, G. Waksman, C. Frieden, and S. J. Hultgren (2000)
PNAS 97, 7709-7714
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