Journal Article

<i>Escherichia coli</i> Uropathogenic-Specific Protein, Usp, Is a Bacteriocin-Like Genotoxin

Damijan Nipič, Zdravko Podlesek, Maruska Budič, Miha črnigoj and Darja Žgur-Bertok

in The Journal of Infectious Diseases

Published on behalf of Infectious Diseases Society of America

Volume 208, issue 10, pages 1545-1552
Published in print November 2013 | ISSN: 0022-1899
Published online August 2013 | e-ISSN: 1537-6613 | DOI: https://dx.doi.org/10.1093/infdis/jit480
Escherichia coli Uropathogenic-Specific Protein, Usp, Is a Bacteriocin-Like Genotoxin

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Background. Bacterial genotoxins provoke DNA damage and carcinogenesis. The Escherichia coli uropathogenic-specific protein gene, usp, and its linked genes, imu1-3, are associated with strains from pyelonephritis, prostatitis, and bacteremia of urinary tract origin. While the Usp C-terminal domain exhibits similarity with DNase-like colicins and pyocins, its role and mechanisms of action, as well as those of the 3 associated proteins, is unknown.

Methods. We isolated Usp and Imu1-3 and examined their activity on plasmid DNA, human umbilical vein endothelial cells, and human embryonic kidney cells (cell line HEK293). The affect of Usp and Imu1-3 was assessed by MTT and Comet assays, infection assays, caspase 3/7 activity, fluorescently labeled actin staining, and Western blotting.

Results. Usp possesses DNase activity and, particularly when coapplied with Imu2, exhibits genotoxic activity in mammalian cells. Infection assays demonstrated that E. coli usp+ imu1-3+ affects the viability of mammalian cells, induces increased caspase 3/7 activity, and perturbs cell cytoskeleton structure.

Conclusions. Usp is a novel E. coli genotoxin active against mammalian cells. Optimal in vivo activity of Usp requires Imu2. Infection with E. coli usp+ imu1-3+ induces a response characteristic of apoptosis.

Keywords: Escherichia coli; uropathogenic specific protein; genotoxin; bacteriocin-like

Journal Article.  4334 words.  Illustrated.

Subjects: Infectious Diseases ; Immunology ; Public Health and Epidemiology ; Microbiology

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