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IAI Accepts, published online ahead of print on 25 August 2008
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Infect. Immun. doi:10.1128/IAI.00122-08
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

ZapA a Virulence Factor in a Rat Model of Proteus mirabilis Induced Acute and Chronic Prostatitis

Van Phan, Robert Belas, Brendan F. Gilmore, and Howard Ceri*

The Biofilm Research Group, Department of Biological Sciences, University of Calgary, 2500 University Drive NW, Calgary, AB, Canada T2N 1N4; Center of Marine Biotechnology, University of Maryland Biotechnology Institute, 701 E. Pratt Street, Baltimore, MD, 21202 USA; School of Pharmacy, Queen's University Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast, BT9 7BL, UK

* To whom correspondence should be addressed. Email: ceri{at}ucalgary.ca.


   Abstract

Our knowledge of pathogenesis has benefited from a better understanding of the role of specific virulence factors in disease. To determine the role of the virulence factor ZapA, a 54-kDa metalloproteinase of Proteus mirabilis, in prostatits rats were either infected with wild type P. mirabilis (WT) or its isogenic ZapA- mutant KW360. WT produced both acute and chronic prostatitis showing the typical histological progressions that are the hallmarks of these diseases. Infection with the ZapA- mutant however resulted in reduced levels of acute prostatitis, as determined from lower levels of tissue damage, bacterial colonization, and inflammation. Further, the ZapA-mutant failed to establish a chronic infection, in that bacteria were cleared from the prostate, inflammation was resolved and tissue was seen to be healing. Clearance from the prostate was not the result of a reduced capacity of the ZapA- mutant to form biofilms in vitro. These finding clearly define ZapA as an important virulence factor in both acute and chronic bacterial prostatitis.







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