Prevalence and antibiotic susceptibility patterns of uropathogens in men with prostate cancer and benign prostate hyperplasia from Southwestern Nigeria.

BACKGROUND: Epidemiological investigations have revealed an important association between infection, inflammation and prostate cancer. Certain bacterial species, such as Klebsiella spp, Escherichia coli, Pseudomonas spp, Proteus mirabilis, Chlamydia trachomatis have been linked to prostate cancer. This study aimed to examine the microbiota; specifically bacterial species that have been linked to prostate infections in the urine of individuals diagnosed with prostate cancer. RESULTS: Sixty-six prostate cancer patients and forty controls provided midstream urine samples. The urine samples were grown on suitable medium, and bacterial isolates were detected by standard microbiological methods. Additionally, the antibiotic sensitivity pattern of the bacterial isolates was analysed. A total of number of 72 bacterial isolates were obtained from the urine of study participants. The results showed the presence of Escherichia coli (50.0%), Pseudomonas aeruginosa (18.1%), Klebsiella spp (15.3%), Staphylococcus aureus (8.3%), Enterobacter spp (4.2%), and Proteus mirabilis (2.8%) in the urine. The most common bacterial species isolated from prostate cancer patients was Escherichia coli, which was susceptible to levofloxacin (100%), tobramycin (91.7%), and amikacin (62.5%). CONCLUSIONS: This study's findings established the presence of bacteria previously linked to prostatitis. This report indicates a high prevalence of pro-inflammatory bacteria and uropathogens in the urinary tract of men diagnosed with prostate cancer.

Different Prostatic Tissue Microbiomes between High- and Low-Grade Prostate Cancer Pathogenesis.

Numerous human pathologies, such as neoplasia, are related to particular bacteria and changes in microbiome constituents. To investigate the association between an imbalance of bacteria and prostate carcinoma, the microbiome and gene functionality from tissues of patients with high-grade prostate tumor (HGT) and low-grade prostate tumor (LGT) were compared utilizing next-generation sequencing (NGS) technology. The results showed abnormalities in the bacterial profiles between the HGT and LGT specimens, indicating alterations in the make-up of bacterial populations and gene functionalities. The HGT specimens showed higher frequencies of Cutibacterium, Pelomonas, and Corynebacterium genera than the LGT specimens. Cell proliferation and cytokine assays also showed a significant proliferation of prostate cancer cells and elevated cytokine levels in the cells treated with Cutibacterium, respectively, supporting earlier findings. In summary, the HGT and LGT specimens showed differences in bacterial populations, suggesting that different bacterial populations might characterize high-grade and low-grade prostate malignancies.

Gut microbiome: a novel preventive and therapeutic target for prostatic disease.

The human gut microbiome (GM) impacts various physiological processes and can lead to pathological conditions and even carcinogenesis if homeostasis is disrupted. Recent studies have indicated a connection between the GM and prostatic disease. However, the underlying mechanisms are still unclear. This review aims to provide a summary of the existing information regarding the connection between the GM and various prostatic conditions such as chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), benign prostatic hyperplasia (BPH), and prostate cancer (PCa). Furthermore, the review aims to identify possible pathogenic mechanisms and suggest potential ways of targeting GM to prevent and treat prostatic disease. Due to the complexity of the mechanism between GM and prostatic diseases, additional research is required to comprehend the association between the two. This will lead to more effective treatment options for prostatic disease.

A prospective evaluation of the prostate microbiome in malignant and benign tissue using transperineal biopsy.

BACKGROUND: The link between the prostate microbiome and prostate cancer remains unclear. Few studies have analyzed the microbiota of prostate tissue, and these have been limited by potential contamination by transrectal biopsy. Transperineal prostate biopsy offers an alternative and avoids fecal cross-contamination. We aim to characterize the prostate microbiome using transperineal biopsy. METHODS: Patients with clinical suspicion for prostate cancer who were to undergo transperineal prostate biopsy with magnetic resonance imaging (MRI) fusion guidance were prospectively enrolled from 2022 to 2023. Patients were excluded if they had Prostate Imaging Reporting and Data System lesions with scores ≤ 3, a history of prostate biopsy within 1 year, a history of prostate cancer, or antibiotic use within 30 days of biopsy. Tissue was collected from the MRI target lesions and nonneoplastic transitional zone. Bacteria were identified using 16S ribosomal RNA gene sequencing. RESULTS: Across the 42 patients, 76% were found to have prostate cancer. Beta diversity indices differed significantly between the perineum, voided urine, and prostate tissue. There were no beta diversity differences between cancerous or benign tissue, or between pre- and postbiopsy urines. There appear to be unique genera more abundant in cancerous versus benign tissue. There were no differences in alpha diversity indices relative to clinical findings including cancer status, grade, and risk group. CONCLUSIONS: We demonstrate a rigorous method to better characterize the prostate microbiome using transperineal biopsy and to limit contamination. These findings provide a framework for future large-scale studies of the microbiome of prostate cancer.

Phenotypic and genomic characterization of a small colony variant of Klebsiella pneumoniae isolated from urine of a prostate cancer case.

Small colony variants (SCVs) in Klebsiella pneumoniae are rare and understudied. We report an SCV of Klebsiella pneumoniae isolated from the urine of a prostate cancer patient undergoing prolonged radiotherapy. The strain was non-lactose fermenting, non-mucoid, slow-growing, multi-drug resistant, and showed atypical biochemical reactions and biofilm formation. On whole genome sequencing, it showed low-level virulence, sequence type 231 and gene CTX-M-15. Three major porins OmpK35, OmpK36 and OmpK37 were found. SCVs pose challenges like difficulties in identification, altered metabolism, and increased biofilm formation, which contribute to persistent infections. Radiotherapy and chemotherapy may have led to the formation of the SCV phenotype.

Influence of microbiome in intraprostatic inflammation and prostate cancer.

BACKGROUND: Chronic infection and inflammation have been linked to the development of prostate cancer. Dysbiosis of the oral and gut microbiomes and subsequent microbial translocation can lead to pathogenic prostate infections. Microbial-produced metabolites have also been associated with signaling pathways that promote prostate cancer development. A comprehensive discussion on the mechanisms of microbiome infection and the prostate microenvironment is essential to understand prostate carcinogenesis. METHODS: Published studies were used from the National Center for Biotechnology Information (NCBI) database to conduct a narrative review. No restrictions were applied in the selection of articles. RESULTS: Microbiome-derived short-chain fatty acids (SCFAs) have been found to upregulate multiple signaling pathways, including MAPK and PI3K, through IGF-1 signaling and M2 macrophage polarization. SCFAs can also upregulate Toll-like receptors, leading to chronic inflammation and the creation of a pro-prostate cancer environment. Dysbiosis of oral microbiota has been correlated with prostate infection and inflammation. Additionally, pathogenic microbiomes associated with urinary tract infections have shown a link to prostate cancer, with vesicoureteral reflux potentially contributing to prostate infection. CONCLUSIONS: This review offers a comprehensive understanding of the impact of microbial infections linked to intraprostatic inflammation as a causative factor for prostate cancer. Further studies involving the manipulation of the microbiome and its produced metabolites may provide a more complete understanding of the microenvironmental mechanisms that promote prostate carcinogenesis.

Cutibacterium acnes invades prostate epithelial cells to induce BRCAness as a possible pathogen of prostate cancer.

BACKGROUND: Abundant evidence suggests that chronic inflammation is linked to prostate cancer and that infection is a possible cause of prostate cancer. METHODS: To identify microbiota or pathogens associated with prostate cancer, we investigated the transcriptomes of 20 human prostate cancer tissues. We performed de novo assembly of nonhuman sequences from RNA-seq data. RESULTS: We identified four bacteria as candidate microbiota in the prostate, including Moraxella osloensis, Uncultured chroococcidiopsis, Cutibacterium acnes, and Micrococcus luteus. Among these, C. acnes was detected in 19 of 20 prostate cancer tissue samples by immunohistochemistry. We then analyzed the gene expression profiles of prostate epithelial cells infected in vitro with C. acnes and found significant changes in homologous recombination (HR) and the Fanconi anemia pathway. Notably, electron microscopy demonstrated that C. acnes invaded prostate epithelial cells and localized in perinuclear vesicles, whereas analysis of γH2AX foci and HR assays demonstrated impaired HR repair. In particular, BRCA2 was significantly downregulated in C. acnes-infected cells. CONCLUSIONS: These findings suggest that C. acnes infection in the prostate could lead to HR deficiency (BRCAness) which promotes DNA double-strand breaks, thereby increasing the risk of cancer development.

The gut microbiome-prostate cancer crosstalk is modulated by dietary polyunsaturated long-chain fatty acids.

The gut microbiota modulates response to hormonal treatments in prostate cancer (PCa) patients, but whether it influences PCa progression remains unknown. Here, we show a reduction in fecal microbiota alpha-diversity correlating with increase tumour burden in two distinct groups of hormonotherapy naïve PCa patients and three murine PCa models. Fecal microbiota transplantation (FMT) from patients with high PCa volume is sufficient to stimulate the growth of mouse PCa revealing the existence of a gut microbiome-cancer crosstalk. Analysis of gut microbial-related pathways in mice with aggressive PCa identifies three enzymes responsible for the metabolism of long-chain fatty acids (LCFA). Supplementation with LCFA omega-3 MAG-EPA is sufficient to reduce PCa growth in mice and cancer up-grading in pre-prostatectomy PCa patients correlating with a reduction of gut Ruminococcaceae in both and fecal butyrate levels in PCa patients. This suggests that the beneficial effect of omega-3 rich diet is mediated in part by modulating the crosstalk between gut microbes and their metabolites in men with PCa.

Current Trends and Challenges of Microbiome Research in Prostate Cancer.

PURPOSE OF REVIEW: The role of the gut microbiome in prostate cancer is an emerging area of research interest. However, no single causative organism has yet been identified. The goal of this paper is to examine the role of the microbiome in prostate cancer and summarize the challenges relating to methodology in specimen collection, sequencing technology, and interpretation of results. RECENT FINDINGS: Significant heterogeneity still exists in methodology for stool sampling/storage, preservative options, DNA extraction, and sequencing database selection/in silico processing. Debate persists over primer choice in amplicon sequencing as well as optimal methods for data normalization. Statistical methods for longitudinal microbiome analysis continue to undergo refinement. While standardization of methodology may help yield more consistent results for organism identification in prostate cancer, this is a difficult task due to considerable procedural variation at each step in the process. Further reproducibility and methodology research is required.

Gut microbiota in patients with prostate cancer: a systematic review and meta-analysis.

BACKGROUND: Increasing evidence indicates that gut microbiota are closely related to prostate cancer. This study aims to assess the gut microbiota composition in patients with prostate cancer compared to healthy participants, thereby advancing understanding of gut microbiota's role in prostate cancer. METHODS: A systematic search was conducted across PubMed, Web of Science, and Embase databases, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The methodological quality of included studies was evaluated using the Newcastle-Ottawa Scale (NOS), and pertinent data were analyzed. The kappa score assessed interrater agreement. RESULTS: This study encompassed seven research papers, involving 250 prostate cancer patients and 192 controls. The kappa was 0.93. Meta-analysis results showed that alpha-diversity of gut microbiota in prostate cancer patients was significantly lower than in the control group. In terms of gut microbiota abundance, the ratio of Proteobacteria, Bacteroidia, Clostridia, Bacteroidales, Clostridiales, Prevotellaceae, Lachnospiraceae, Prevotella, Escherichia-Shigella, Faecalibacterium, and Bacteroides was higher in prostate cancer patients. Conversely, the abundance ratio of Actinobacteria, Bacteroidetes, Firmicutes, Selenomonadales, Veillonella, and Megasphaera was higher in the control group. CONCLUSION: Our study reveals differences in alpha-diversity and abundance of gut microbiota between patients with prostate cancer and controls, indicating gut microbiota dysbiosis in those with prostate cancer. However, given the limited quality and quantity of selected studies, further research is necessary to validate these findings.

Prostate Infiltration by Treg and Th17 Cells as an Immune Response to Propionibacterium acnes Infection in the Course of Benign Prostatic Hyperplasia and Prostate Cancer.

Benign prostatic hyperplasia (BPH) and prostate cancer (PCa) belong to the most frequent diseases in ageing men. It has been proposed that prostate chronic inflammation is a risk factor for the development of both BPH and PCa. However, potential stimuli that cause or maintain inflammation in the prostate gland are still poorly characterized. Bacterial infections seems to be one of the potential sources of prostatitis. Recent studies show that Propionibacterium acnes (P. acnes) is the most prevalent microorganism in the prostate gland and may be a predisposing factor for inflammation of prostatic tissue. It indicates that P. acnes may contribute to cancer development by enhancing proinflammatory responses, as well as by modifying the prostate extracellular environment. In this review, we discuss the potential role of P. acnes in the development of BPH and PCa and highlight the importance of regulatory T CD4(+)FoxP3(+) (Treg) and Th17 cells in response to P. acnes infection in the context of both prostate diseases.

Life style and interaction with microbiota in prostate cancer patients undergoing radiotherapy: study protocol for a randomized controlled trial.

BACKGROUND: Prostate cancer (PCa) is the second most common cancer in men worldwide. The standard non-surgical approach for localized PCa is radiotherapy (RT), but one of the limitations of high-dose RT is the potential increase in gastrointestinal and genitourinary toxicities. We present the protocol of the Microstyle study, a multicentre randomized two-arm crossover clinical trial. The primary outcome will be assessed at the end of 6-month intervention, by measuring the change in adherence to a healthy lifestyle score. The hypothesis is that modifying lifestyle we change microbiome and improve quality of life and decrease side effects of RT. METHODS: Study participants will be recruited among men undergoing RT in two Italian centers (Milan and Naples). We foresee to randomize 300 patients in two intervention arms: Intervention Group (IG) and Control Group (CG). Participants allocated to the IG will meet a dietitian and a physiotherapist before RT to receive personalized diet and exercise recommendations, according to their health status, to improve overall lifestyle and reduce side effects (bowel and/or urinary problems). Dietitian and physiotherapist will work together to set individualized goals to reduce or eliminate side effects and pain according to their health status. All participants (IG) will be given a pedometer device (steps counter) in order to monitor and to spur participants to increase physical activity and reduce sedentary behavior. Participants included in the CG will receive baseline general advice and materials available for patients undergoing RT. According to the cross-over design, the CG will cross to the intervention approach after 6-month, to actively enhance compliance towards suggested lifestyle recommendations for all patients. DISCUSSION: This trial is innovative in its design because we propose a lifestyle intervention during RT, that includes both dietary and physical activity counselling, as well as monitoring changes in microbiome and serum biomarkers. The promotion of healthy behaviour will be initiated before initiation of standard care, to achieve long lasting effects, controlling side effects, coping with feelings of anxiety and depression and improve efficacy of RT. TRIAL REGISTRATION: ClincalTrial.gov registration number: NCT05155618 . Retrospectively registered on December 13, 2021. The first patient was enrolled on October 22, 2021.

Specific Gut Microbial Environment in Lard Diet-Induced Prostate Cancer Development and Progression.

Lard diet (LD) is a risk factor for prostate cancer (PCa) development and progression. Two immunocompetent mouse models fed with isocaloric specific fat diets (LD) enriched in saturated and monounsaturated fatty acid (SMFA), showed significanftly enhanced PCa progression with weight gain compared with a fish oil diet (FOD). High gut microbial divergency resulted from difference in diets, and the abundance of several bacterial species, such as in the orders Clostridiales and Lactobacillales, was markedly altered in the feces of LD- or FOD-fed mice. The proportion of the order Lactobacillales in the gut was negatively involved in SMFA-induced body weight gain and PCa progression. We found the modulation of lipid metabolism and cholesterol biosynthesis pathways with three and seven commonly up- and downregulated genes in PCa tissues, and some of them correlated with the abundance of the order Lactobacillales in mouse gut. The expression of sphingosine 1-phosphate receptor 2, which is associated with the order Lactobacillales and cancer progression in mouse models, was inversely associated with aggressive phenotype and weight gain in patients with PCa using the NCBI Gene Expression Omnibus database. Therefore, SMFA may promote PCa progression with the abundance of specific gut microbial species and overexpression of lipogenic genes in PCa. Therapeutics with alteration of gut microbiota and candidate genes involved in diet-induced PCa progression may be attractive in PCa.

Differential Circulating Fungal Microbiome in Prostate Cancer Patients Compared to Healthy Control Individuals.

BACKGROUNDS: Infection and inflammation play an important role in prostate cancer (PCa) etiology and pathogenesis. However, the environmental drivers for PCa are not fully understood. METHODS: In a cross-sectional study, we analyzed circulating fungal microbiome in plasma samples from age and race-matched healthy control men (n = 34) and preoperative PCa patients (n = 31). RESULTS: The fungal community in the plasma exhibited differences between individuals with PCa and healthy controls according to the beta diversity; there was no difference in the alpha diversity. Moreover, the relative abundance of several fungi differed between the two study groups from the class to species levels. The most significant differences were Filobasidiales family, Pyronemataceae family, and Cryptococcus ater species, which were enriched in PCa patients compared to controls. The increased Bipolaris genus was associated with low prostate-specific antigen (PSA) levels, increased Sordariomycetes class was associated with severe pathological stage, and decreased Phoma herbarum species was associated with disease relapse, compared to corresponding controls. Several fungi from class to species levels were increased in the controls compared to patients. CONCLUSION: This is the first study to show plasma distinct fungal microbiome and its associations with PSA levels, relapse, and pathology stages in PCa patients.

Cutibacterium acnes Induces the Expression of Immunosuppressive Genes in Macrophages and is Associated with an Increase of Regulatory T-Cells in Prostate Cancer.

Tumors and infectious agents both benefit from an immunosuppressive environment. Cutibacterium acnes (C. acnes) is a bacterium in the normal skin microbiota, which has the ability to survive intracellularly in macrophages and is significantly more common in prostate cancer tissue compared with normal prostate tissue. This study investigated if prostate cancer tissue culture positive for C. acnes has a higher infiltration of regulatory T-cells (Tregs) and if macrophages stimulated with C. acnes induced the expression of immunosuppressive genes that could be linked to an increase of Tregs in prostate cancer. Real-time PCR and enzyme-linked immunosorbent spot assay (ELISA) were used to examine the expression of immunosuppressive genes in human macrophages stimulated in vitro with C. acnes, and associations between the presence of C. acnes and infiltration of Tregs were investigated by statistically analyzing data generated in two previous studies. The in vitro results demonstrated that macrophages stimulated with C. acnes significantly increased their expression of PD-L1, CCL17, and CCL18 mRNA and protein (p <0.05). In the cohort, Tregs in tumor stroma and tumor epithelia were positively associated with the presence of C. acnes (P = 0.0004 and P = 0.046, respectively). Since the macrophages stimulated with C. acnes in vitro increased the expression of immunosuppressive genes, and prostate cancer patients with prostatic C. acnes infection had higher infiltration of Tregs than their noninfected counterparts, we suggest that C. acnes may contribute to an immunosuppressive tumor environment that is vital for prostate cancer progression. IMPORTANCE In an immune suppressive tumor microenvironment constituted by immunosuppressive cells and immunosuppressive mediators, tumors may improve their ability to give rise to a clinically relevant cancer. In the present study, we found that C. acnes might contribute to an immunosuppressive environment by recruiting Tregs and by increasing the expression of immunosuppressive mediators such as PD-L1, CCL17, and CCL18. We believe that our data add support to the hypothesis of a contributing role of C. acnes in prostate cancer development. If established that C. acnes stimulates prostate cancer progression it may open up avenues for targeted prostate cancer treatment.

The 27th Annual Prostate Cancer Foundation Scientific Retreat Report.

BACKGROUND: The 27th Annual Prostate Cancer Foundation (PCF) Scientific Retreat was held virtually from October 20 to 23, 2020. METHODS: The Annual PCF Scientific Retreat is a global scientific research conference that highlights the most promising and cutting edge advances in prostate cancer basic, translational and clinical research, as well as research from other fields with a strong potential for advancing prostate cancer research. RESULTS: Primary areas of research discussed at the 2020 PCF Retreat included: (i) the intersection between prostate cancer and COVID-19 research; (ii) lessons from the COVID-19 pandemic that may address prostate cancer disparities; (iv) the role of the microbiome in cancer; (v) current challenges in treatment of patients with metastatic prostate cancer; (viii) prostate cancer germline genetics and evolutionary genomics; (ix) advances in circulating DNA methylation biomarkers for diagnosis, prognosis, and treatment selection; (x) advances in the development of MYC-targeting therapeutics; (xi) advances in antibody-drug conjugates for the treatment of cancer; (xii) advances for immunotherapy in prostate cancer; and (xiii) updates from other recent prostate cancer clinical trials. CONCLUSIONS: This article summarizes the research presented at the 2020 PCF Scientific Retreat. We hope that dissemination of this knowledge will help to accelerate and direct the next major advances in prostate cancer research and care.

Increase in Akkermansiaceae in Gut Microbiota of Prostate Cancer-Bearing Mice.

Gut microbiota are reported to be associated with many diseases, including cancers. Several bacterial taxa have been shown to be associated with cancer development or response to treatment. However, longitudinal microbiota alterations during the development of cancers are relatively unexplored. To better understand how microbiota changes, we profiled the gut microbiota composition from prostate cancer-bearing mice and control mice at five different time points. Distinct gut microbiota differences were found between cancer-bearing mice and control mice. Akkermansiaceae was found to be significantly higher in the first three weeks in cancer-bearing mice, which implies its role in the early stage of cancer colonization. We also found that Bifidobacteriaceae and Enterococcaceae were more abundant in the second and last sampling week, respectively. The increments of Akkermansiaceae, Bifidobacteriaceae and Enterococcaceae were previously found to be associated with responses to immunotherapy, which suggests links between these bacteria families and cancers. Additionally, our function analysis showed that the bacterial taxa carrying steroid biosynthesis and butirosin and neomycin biosynthesis were increased, whereas those carrying naphthalene degradation decreased in cancer-bearing mice. Our work identified the bacteria taxa altered during prostate cancer progression and provided a resource of longitudinal microbiota profiles during cancer development in a mouse model.

The Firmicutes/Bacteroidetes ratio of the human gut microbiota is associated with prostate enlargement.

BACKGROUND: The pathophysiology of the prostate enlargement underlying lower urinary tract symptoms is unknown. Meanwhile, the gut microbiota can contribute to various host conditions. We hypothesized that the gut microbiota plays a role in prostate enlargement. METHODS: We included 128 patients who underwent prostate biopsies at our hospitals between December 2018 and March 2020, excluding those who had used antibiotics within the past 6 months and those who were diagnosed with prostate cancer of cT3 or higher. Patients with prostate volumes ≥30 ml were defined as the prostate-enlargement (PE) group; those with prostate volumes <30 ml were defined as the non-PE group. Their gut microbiotas were analyzed via 16S rRNA metagenomic analyses of rectal swab samples and were compared between the groups. RESULTS: The PE group included 66 patients; the non-PE group included 62 patients. Age, body mass index, and prostate-specific antigen levels did not significantly differ between the groups. Linear discriminant analysis effect size analysis indicated a higher proportion of Firmicutes and Actinobacteria in the PE group and a higher proportion of Bacteroidetes in the non-PE group. The Firmicutes/Bacteroidetes (F/B) ratio was significantly higher in the PE group than in the non-PE group (2.21 ± 0.39 vs. 1.61 ± 0.40, p = 0.015). CONCLUSION: The F/B ratio of the gut microbiota was associated with prostate enlargement. Although the detailed mechanisms are unclear, the gut microbiota might affect prostate enlargement.

Oncogenic gene fusions in nonneoplastic precursors as evidence that bacterial infection can initiate prostate cancer.

Prostate adenocarcinoma is the second most commonly diagnosed cancer in men worldwide, and the initiating factors are unknown. Oncogenic TMPRSS2:ERG (ERG+) gene fusions are facilitated by DNA breaks and occur in up to 50% of prostate cancers. Infection-driven inflammation is implicated in the formation of ERG+ fusions, and we hypothesized that these fusions initiate in early inflammation-associated prostate cancer precursor lesions, such as proliferative inflammatory atrophy (PIA), prior to cancer development. We investigated whether bacterial prostatitis is associated with ERG+ precancerous lesions in unique cases with active bacterial infections at the time of radical prostatectomy. We identified a high frequency of ERG+ non-neoplastic-appearing glands in these cases, including ERG+ PIA transitioning to early invasive cancer. These lesions were positive for ERG protein by immunohistochemistry and ERG messenger RNA by in situ hybridization. We additionally verified TMPRSS2:ERG genomic rearrangements in precursor lesions using tricolor fluorescence in situ hybridization. Identification of rearrangement patterns combined with whole-prostate mapping in three dimensions confirmed multiple (up to eight) distinct ERG+ precancerous lesions in infected cases. We further identified the pathogen-derived genotoxin colibactin as a potential source of DNA breaks in clinical cases as well as cultured prostate cells. Overall, we provide evidence that bacterial infections can initiate driver gene alterations in prostate cancer. In addition, our observations indicate that infection-induced ERG+ fusions are an early alteration in the carcinogenic process and that PIA may serve as a direct precursor to prostate cancer.

Carnobacterium inhibens isolated in blood culture of an immunocompromised, metastatic cancer patient: a case report and literature review.

BACKGROUND: Carnobacterium species are lactic acid-producing Gram-positive bacteria that have been approved by the US Food and Drug Administration and Health Canada for use as a food bio-preservative. The use of live bacteria as a food additive and its potential risk of infections in immunocompromised patients are not well understood. CASE PRESENTATION: An 81-year-old male with a history of metastatic prostate cancer on androgen deprivation therapy and chronic steroids presented to our hospital with a 2-week history of productive cough, dyspnea, altered mentation, and fever. Extensive computed tomography imaging revealed multifocal pneumonia without other foci of infection. He was diagnosed with pneumonia and empirically treated with ceftriaxone and vancomycin. Blood cultures from admission later returned positive for Carnobacterium inhibens. He achieved clinical recovery with step-down to oral amoxicillin/clavulanic acid for a total 7-day course of antibiotics. CONCLUSIONS: This is the fourth reported case of bacteremia with Carnobacterium spp. isolated from humans. This case highlights the need to better understand the pathogenicity and disease spectrum of bacteria used in the food industry for bio-preservation, especially in immunocompromised patients.