NDLI: Antibodies against Hemolysin and Cytotoxic Necrotizing Factor Type 1 (CNF1) Reduce Bladder Inflammation in a Mouse Model of Urinary Tract Infection with Toxigenic Uropathogenic Escherichia coli

Content Provider	PubMed Central
Author	Smith, Mark A. Weingarten, Rebecca A. Russo, Lisa M. Ventura, Christy L. O'brien, Alison D.
Editor	Payne, S. M.
Copyright Year	2015
Abstract	Uropathogenic Escherichia coli (UPEC) is the leading cause of cystitis. Cytotoxic necrotizing factor 1 (CNF1) and hemolysin (Hly) are toxins made by approximately 50% of UPEC isolates. CNF1 and Hly contribute to the robust inflammatory response in the bladders of mice challenged with UPEC strain CP9. We hypothesized that antibodies against CNF1 and/or Hly would reduce cystitis caused by CP9. To test this theory, we immunized female C3H/HeOuJ mice subcutaneously with a genetically derived Hly toxoid or genetically derived CNF1 toxoid plus sublethal doses of CNF1. We collected serum and observed increasing titers of specific and neutralizing antibodies against Hly or CNF1 over time. We challenged the mice intraurethrally with CP9 and euthanized them 24 h later. We observed 10-fold lower bacterial titers in the urine of Hly-immunized mice than in that of sham-immunized mice but no difference in kidney bacterial titers. Immunized mice also exhibited significantly less cystitis than sham-immunized mice. In CNF1-vaccinated mice, we detected neither a difference in urine or kidney bacterial titers nor a reduction in the severity of cystitis versus that of sham-immunized mice. We then passively administered an anti-CNF1 monoclonal antibody intraperitoneally to female C3H/HeOuJ mice prior to intraurethral challenge with CP9. Upon challenge, we noted no difference in colonization of the urine or kidney; however, cystitis was reduced significantly in mice treated with the anti-CNF1 antibody versus that in the bladders of mice given an isotype control antibody. Taken together, our data demonstrate that antibodies against CNF1 or Hly reduce the bladder pathology caused by UPEC.
Related Links	http://dx.doi.org/10.1128/IAI.02848-14
Ending Page	1673
Page Count	13
Starting Page	1661
File Format	PDF
ISSN	10985522
e-ISSN	10985522
Journal	Infection and Immunity
Issue Number	4
Volume Number	83
Language	English
Publisher	American Society for Microbiology
Publisher Date	2015-04-01
Access Restriction	Open
Rights Holder	American Society for Microbiology
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Infectious Diseases Parasitology Immunology Microbiology

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