Successful use of a phage endolysin for treatment of chronic pelvic pain syndrome/chronic bacterial prostatitis

Abstract

Chronic prostatitis (CP) is a common inflammatory condition of the prostate that is estimated to effect 2%-10% of the world's male population. It can manifest as perineal, suprapubic, or lower back pain and urinary symptoms occurring with either recurrent bacterial infection [chronic bacterial prostatitis (CBP)] or in the absence of evidence of bacterial infection [chronic pelvic pain syndrome (CPPS)]. Here, in the case of a 39 years-old CBP patient, we report the first successful use of a bacteriophage-derived muralytic enzyme (endolysin) to treat and resolve the disease. Bacteriological analysis of the patient's prostatic secretion and semen samples revealed a chronic Enterococcus faecalis prostate infection, supporting a diagnosis of CBP. The patient's E. faecalis strain was resistant to several antibiotics and developed resistance to others during the course of treatment. Previous treatment with multiple courses of antibiotics, bacteriophages, probiotics, and immunologic stimulation had failed to achieve long term eradication of the infection or lasting mitigation of the symptoms. A cloned endolysin gene, encoded by E. faecalis bacteriophage ϕEf11, was expressed, and the resulting gene product was purified to electrophoretic homogeneity. A seven-day course of treatment with the endolysin resulted in the elimination of the E. faecalis infection to below culturally detectable levels, and the abatement of symptoms to near normal levels. Furthermore, during the endolysin treatment, the patient experienced no untoward reactions. The present report demonstrates the effectiveness of an endolysin as a novel modality in managing a recalcitrant infection that could not be controlled by conventional antibiotic therapy.

Keywords: Enterococcus faecalis; antibiotic resistance; bacteriophage; chronic bacterial prostatitis; endolysin therapy.

Figure 1

Timeline of the most relevant attacks, diagnostic procedures, microbiological results (dark blue), antibiotic therapies (dark grey), Enterococcus faecalis vaccination (light blue), phage therapy (magenta), endolysin therapy (red), and other supportive therapies (green). “Microbiology” refers to microbiological analysis determining the presence (E. faecalis⁺) or absence (E. faecalis⁻) of detectable E. faecalis infection.

Figure 2

Spot testing sensitivity of E. faecalis strain (587A2) from the CBP patient to purified phage ORF28 endolysin. Dilutions of purified endolysin (original concentration = 800 μg/mL) spotted onto a soft-agar lawn of E. faecalis 587A2. Lytic zones observed after overnight incubation @ 37°C. Numbers towards center of plate indicate the concentration (μg/mL) of ORF28 applied in each section of the plate. Lytic zone observable down to endolysin concentration of 0.4 μg/mL.

Figure 3

SDS-PAGE analysis of purified ORF28 endolysin. Note single 46.1 kDa band from affinity-purified ORF28 endolysin.