Direct Visualization ofPropionibacterium acnesin Prostate Tissue by Multicolor Fluorescent In Situ Hybridization Assay

Abstract

Prostate tissues from patients with prostate cancer and benign prostatic hyperplasia (BPH) frequently contain histological inflammation, and a proportion of these patients show evidence of Propionibacterium acnes infection in the prostate gland. We developed a multicolor fluorescent in situ hybridization (FISH) assay targeting P. acnes 23S rRNA along with a 14-kb region of the P. acnes genome. This assay was used to analyze prostate tissues from patients with prostate cancer and BPH. P. acnes infection of the prostate gland was demonstrated in prostatic tissue in 5 of 10 randomly selected prostate cancer patients. FISH analysis and confocal laser microscopy imaging revealed intracellular localization and stromal biofilmlike aggregates as common forms of P. acnes infection in prostate tissues from both prostate cancer and BPH patients. A sequential analysis of prostate tissue from individual patients suggested that P. acnes can persist for up to 6 years in the prostate gland. These results indicate that P. acnes can establish a persistent infection in the prostate gland. Further study is needed to clarify the link between this bacterium and prostatic inflammation which may contribute to the development of BPH and prostate cancer.Clinical benign prostatic hyperplasia (BPH) occurs in half of all men by the age of 80 years (20), while prostate cancer is a leading cause of morbidity and death among men in the United States and Western Europe (13). Chronic or recurrent inflammation has been implicated in the development and progression of both BPH (20) and prostate cancer (9,24,25,30), and various degrees of histological inflammation are seen in the majority of prostate tissue specimens examined. The possibility of an infectious etiology for this prostatic inflammation has been raised in the context of both BPH (20) and prostate cancer, although the accumulation of a larger amount of evidence supports this hypothesis for the latter. For example, epidemiological studies have reported an increased risk of prostate cancer in patients with a history of sexually transmitted infections (29,31,32). The genetic signatures of bacteria were found in prostate tissues from 21 of 107 patients with prostate cancer (21). Moreover, a positive correlation between prostatic inflammation and the detection of bacterial 16S rRNA gene sequences in tissue specimens obtained by radical prostatectomy has been reported (16).Recently, a single bacterial species, Propionibacterium acnes, has been shown to infect a considerable proportion (35%) of prostate glands removed at radical prostatectomy (6). Moreover, the presence of P. acnes was strongly correlated with histological inflammation, suggesting that this bacterium might be linked to cancer development. The possible involvement of P. acnes in prostate pathology was further highlighted by the detection of P. acnes 16S rRNA gene sequences in BPH tissues, with a positive association between the detection of P. acnes DNA and subsequent prostate cancer development reported (1). We have developed ...

A novel multilocus sequence typing scheme for the opportunistic pathogen Propionibacterium acnes and characterization of type I cell surface-associated antigens

“…The organism is an opportunistic pathogen most widely known for its association with acne vulgaris (Dessinioti & Katsambas, 2010) but it also causes bacterial keratitis (Ovodenko et al, 2009) and endophthalmitis after ophthalmic surgery (Javey et al, 2010), and is increasingly recognized as a significant cause of medical device-related infections (Tunney et al, 1999;Zeller et al, 2007;Piper et al, 2009). It has also been linked to synovitis-acne-pustulosis-hyperostosis-osteitis (SAPHO) syndrome (Schaeverbeke et al, 1998), sarcoidosis (Yasuhara et al, 2005;Eishi et al, 2002), primary biliary cirrhosis (Harada et al, 2001), sciatica (Stirling et al, 2001), spondylodiscitis (Uçkay et al, 2010) and, more recently, prostate cancer (Cohen et al, 2005;Alexeyev et al, 2007). The pathogenic potential of P. acnes has been vividly demonstrated from completed genome sequences which reveal a wide range of gene products that may invoke inflammation, degrade host molecules and facilitate evasion of the host immune response (Brüggemann et al, 2004).…”

Dairy Propionibacteria: Less Conventional Probiotics to Improve the Human and Animal Health

“…Recently, a multicolor fluorescent in situ hybridization (FISH) assay targeting the 16S rRNA [30] or 23S rRNA [31] of P.acnes was developed and used to detect this bacterium in blood samples and tissues of patients with prostate cancer, respectively. A FISH protocol and oligonucleotide probes targeting the 16S rRNA of dairy propionibacteria were developed in our laboratory [32] and successfully used for enumeration of P. acidipropionici in cecal samples of mice fed with a strain of this species [33].…”

Multilocus Sequence Typing and Phylogenetic Analysis of Propionibacterium acnes

“…Recently, P. acnes has been associated with prostate cancer due to its prevalence in affected prostate tissue, but its possible etiologic role has yet to be defined (1,7,9).…”