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Induction of Different Apoptosis Pathways by Two Proteus mirabilis Clinical Isolates Strains in Prostatic Epithelial
Alessandra Fusco1, Vittoria Savio1, Anna De Filippis1
1Department of Experimental Medicine, Section of Microbiology and Clinical Microbiology, University of Campania Luigi Vanvitelli, Naples, Italy.
Abstract:
Bacterial prostatitis is believed to be the leading cause of recurrent urinary tract infections (UTIs) in men under 50 years of age and occurs both as an acute febrile disease responsive to antibiotics and as a chronic infection that is often unresponsive to antibiotic treatment. Proteus mirabilis is more commonly associated with UTIs in these abnormalities, especially in patients undergoing catheterisation. This pathogen is able to colonise the host's tissues and to cause disease thanks to the production of many virulence factors such as fimbriae, flagella, immune avoidance, host-damaging factors, and the ability to form crystalline biofilms. In addition, Proteus lipid A may exhibit apoptotic activity and induce desquamation of epithelial cells. The aim of this work was to evaluate the ability of two clinically isolated strains of P. mirabilis that are phenotypically different, named PM1 of PM2, respectively, to induce apoptosis in human prostatic adenocarcinoma PC-3. Our results demonstrate that PM1 and PM2 are able to activate two different apoptotic pathways, and this different behaviour is confirmed by the expression level of the ZapA gene, molecular fingerprinting and different spectrum of antibiotic resistance. The identification and knowledge of relations between the microorganism and host may provide the basis for new solutions to clinical problems with regard to diagnosis and therapy.
Insights
Proteus mirabilis, a common cause of recurrent urinary tract infections (UTIs), can induce apoptosis in human prostate cells through distinct pathways. Understanding these mechanisms is key for developing new diagnostic and therapeutic strategies.
Area of Science:
- Microbiology
- Cell Biology
- Urology
Background:
- Bacterial prostatitis, often caused by Proteus mirabilis, is a leading cause of recurrent urinary tract infections (UTIs) in men under 50.
- Proteus mirabilis utilizes various virulence factors, including fimbriae, flagella, and biofilm formation, to colonize host tissues and cause disease.
- Proteus lipid A can induce apoptosis and epithelial cell desquamation, contributing to disease pathogenesis.
Purpose of the Study:
- To investigate the ability of two distinct clinical isolates of Proteus mirabilis (PM1 and PM2) to induce apoptosis in human prostatic adenocarcinoma PC-3 cells.
- To analyze the molecular mechanisms and phenotypic differences underlying the apoptotic activity of these P. mirabilis strains.
Main Methods:
- Co-culture of human prostatic adenocarcinoma PC-3 cells with two phenotypically different P. mirabilis strains (PM1 and PM2).
- Assessment of apoptosis induction through various assays.
- Analysis of ZapA gene expression levels.
- Molecular fingerprinting.
- Determination of antibiotic resistance profiles.
Main Results:
- Both PM1 and PM2 strains of P. mirabilis induced apoptosis in PC-3 cells via two distinct pathways.
- Differences in apoptotic pathway activation were correlated with ZapA gene expression levels.
- Molecular fingerprinting and antibiotic resistance patterns further differentiated the two P. mirabilis strains.
Conclusions:
- The study demonstrates that different P. mirabilis strains can elicit distinct apoptotic responses in human prostate cells.
- Understanding these strain-specific interactions and molecular differences is crucial for advancing the diagnosis and treatment of bacterial prostatitis and associated UTIs.
- This research provides a foundation for developing targeted therapeutic strategies against P. mirabilis-induced prostatitis.
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