A prostate derived commensal Staphylococcus epidermidis strain prevents and ameliorates induction of chronic prostatitis by UPEC infection

Stephen F Murphy,Joseph D Done,Anthony J Schaeffer,Christel Hall,Praveen Thumbikat

doi:10.1038/s41598-018-35818-1

Stephen F Murphy, Joseph D Done + Show 3 more

Open Access

https://doi.org/10.1038/s41598-018-35818-1

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Journal: Scientific Reports	Publication Date: Nov 27, 2018
Citations: 2	License type: open-access

Affiliation: Northwestern University

Abstract

Chronic prostatitis/Chronic pelvic pain syndrome (CP/CPPS) is a common syndrome with limited therapies and an unknown etiology. Previously, our laboratory has defined a potential role for pathogenic infection in disease onset. Intra-urethral infection with a uropathogenic Escherichia coli strain isolated from a CP/CPPS patient, CP1, induces prostatic inflammation and tactile allodynia in mice. We have also demonstrated that a prostate specific Staphylococcus epidermidis bacterial isolate, NPI (non-pain inducing), from a healthy subject reduces pain and inflammation in an experimental autoimmune prostatitis (EAP) murine model. Here we focus on the interplay between these human isolates in the context of prostatitis development and resolution. NOD/ShiLtJ mice were inoculated with either NP1 or CP1, or combinations of both. Infection with CP1 induced pelvic tactile allodynia after 7 days, while NPI instillation alone induced no such response. Instillation with NPI 7 days following CP1 infection resolved pelvic tactile allodynia and prophylactic instillation 7 days prior to CPI infection prevented its onset. Prophylactic NPI instillation also prevented CP1 colonization of both prostate and bladder tissues. In vitro analyses revealed that CP1 and NPI do not directly inhibit the growth or invasive potential of one another. Immunological analyses revealed that specific markers associated with CP1-induced pelvic allodynia were decreased upon NPI treatment or repressed by prophylactic colonization. This study demonstrates that a commensal bacterial isolate can inhibit the colonization, pain responses, and immunological activation to uropathogenic bacteria, emphasizing the power of a healthy prostatic microflora in controlling health and disease.

Highlights

Prostatitis is a common medical complaint among men of all ages, accounting for over 2 million urology clinic visits each year in the U.S alone[1]
In our xenogeneic experimental autoimmune prostatitis (EAP) murine model of CP/CPPS14, we have shown that Non Pain-Inducing (NPI) has the capacity to ameliorate EAP-induced pelvic tactile allodynia and immune activation, via increased expression of the negative regulators of the adaptive immune response, PDL1 and PDL29
The NPI bacterial strain is capable of ameliorating tactile allodynia and prostatic inflammation in an EAP model of CP/CPPS9

Summary

Introduction

Prostatitis is a common medical complaint among men of all ages, accounting for over 2 million urology clinic visits each year in the U.S alone[1]. Using the prostate-derived S. epidermidis we have previously shown that this strain can efficiently colonize mouse prostate and bladder tissues[9] and does not induce prostate inflammation or pelvic tactile allodynia in either NOD or C57BL/6 mice[9]. We have demonstrated that this NPI strain is distinct from another S. epidermidis strain (7244) isolated from CP/CPPS patient prostate secretions[13], in the ability to induce and modulate pain responses. In our xenogeneic experimental autoimmune prostatitis (EAP) murine model of CP/CPPS14, we have shown that NPI has the capacity to ameliorate EAP-induced pelvic tactile allodynia and immune activation, via increased expression of the negative regulators of the adaptive immune response, PDL1 and PDL29. Taken together this study identifies the potential roles of prostate specific bacterial strains to be either harmful or beneficial to male urological health

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