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Published on: January 16, 2013
ZapA, a virulence factor in a rat model of Proteus mirabilis-induced acute and chronic prostatitis
Van Phan1, Robert Belas, Brendan F Gilmore
1Biofilm Research Group, Department of Biological Sciences, University of Calgary, Calgary, Alberta, Canada T2N 1N4.
Abstract:
Our knowledge of pathogenesis has benefited from a better understanding of the roles of specific virulence factors in disease. To determine the role of the virulence factor ZapA, a 54-kDa metalloproteinase of Proteus mirabilis, in prostatitis, rats were infected with either wild-type (WT) P. mirabilis or its isogenic ZapA(-) mutant KW360. The 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.
Insights
Proteus mirabilis metalloproteinase ZapA is crucial for causing acute and chronic prostatitis in rats. Deleting ZapA significantly reduced disease severity and allowed bacterial clearance, highlighting its role in pathogenesis.
Area of Science:
- Microbiology
- Pathogenesis
- Urology
Background:
- Understanding virulence factors is key to studying disease pathogenesis.
- Proteus mirabilis is a common cause of urinary tract infections, including prostatitis.
Purpose of the Study:
- To investigate the role of the metalloproteinase ZapA from Proteus mirabilis in the development of prostatitis.
- To determine if ZapA is essential for both acute and chronic prostatitis.
Main Methods:
- Rats were infected with wild-type (WT) P. mirabilis or its isogenic ZapA-deficient mutant (ZapA(-)).
- Histological analysis and bacterial colonization levels were assessed to evaluate prostatitis severity.
- In vitro biofilm formation capacity of the mutant was tested.
Main Results:
- WT P. mirabilis infection led to acute and chronic prostatitis with characteristic histological changes.
- Infection with the ZapA(-) mutant resulted in significantly reduced acute prostatitis, evidenced by less tissue damage, lower bacterial load, and decreased inflammation.
- The ZapA(-) mutant was unable to establish chronic infection, with bacteria being cleared and prostate tissue healing.
- The reduced virulence of the ZapA(-) mutant was not due to impaired in vitro biofilm formation.
Conclusions:
- ZapA is a critical virulence factor for Proteus mirabilis in establishing both acute and chronic bacterial prostatitis.
- Targeting ZapA may be a potential therapeutic strategy for prostatitis.
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