Cutibacterium Species Valvular and Cardiac Device-Related Infective Endocarditis: Contemporary Data From the GAMES Prospective Cohort (2008-2023).

BACKGROUND: Information on infective endocarditis (IE) caused by Cutibacterium spp. is limited and new Duke-International Society for Cardiovascular Infectious Diseases (ISCVID) criteria have not yet been properly assessed. We examined clinical characteristics, outcomes, and performance of diagnostic tests for Cutibacterium valvular and cardiac implantable electronic device-related IE (CIED-IE). METHODS: Data corresponding to all episodes of Cutibacterium IE recorded from 2008 to 2023 in a prospective national cohort including 46 Spanish hospitals were examined. Possible IE cases were reassessed using the new criteria. The sensitivity of blood cultures, valvular and CIED cultures, and polymerase chain reaction of the 16S rRNA gene and sequencing (16SPCR) was evaluated. RESULTS: Of 6692 episodes of IE, 67 (1%) were caused by Cutibacterium spp. with 85% affecting men. Of these, 50 were valve-related (45 prosthetic, 5 native) and 17 CIED-related. The new criteria identified 8 additional cases and reclassified 15 as definite IE. Intracardiac complications (abscess, pseudoaneurysm, perforation, or intracardiac fistula) occurred in 23 of 50 (46%) valvular IE episodes, leading to 18% mortality, and up to 40% mortality if surgery was indicated but could not be performed. All CIED-IE cases underwent device removal and no deaths were recorded. Positive diagnosis rates for blood cultures, valve/device cultures, and 16SPCR were 52%, 70%, and 82%, respectively. CONCLUSIONS: Cutibacterium IE is a rare yet potentially life-threatening condition that warrants a high index of suspicion in men with endovascular prosthetic material. The new Duke-ISCVID criteria and molecular techniques are useful for its diagnosis. Considering a significant complication rate, cardiac surgery and removal of CIEDs play a key role in reducing mortality.

Cutibacterium acnes-derived extracellular vesicles promote tumor growth in renal cell carcinoma.

Bacterial flora are present in various parts of the human body, including the intestine, and are thought to be involved in the etiology of various diseases such as multiple sclerosis, intestinal diseases, cancer, and uterine diseases. In recent years, the presence of bacterial 16S rRNA genes has been revealed in blood, which was previously thought to be a sterile environment, and characteristic blood microbiomes have been detected in various diseases. However, the mechanism and the origin of the bacterial information are unknown. In this study, we performed 16S rRNA metagenomic analysis of bacterial DNA in serum extracellular vesicles from five healthy donors and seven patients with renal cell carcinoma and detected Cutibacterium acnes DNA as a characteristic bacterial DNA in the serum extracellular vesicles of patients with renal cell carcinoma. In addition, C. acnes DNA was significantly reduced in postoperative serum extracellular vesicles from patients with renal cell carcinoma compared with that in preoperative serum extracellular vesicles from these patients and was also detected in tumor tissue and extracellular vesicles from tumor tissue-associated microbiota, suggesting an association between C. acnes extracellular vesicles and renal cell carcinoma. C. acnes extracellular vesicles were taken up by renal carcinoma cells to enhance their proliferative potential. C. acnes extracellular vesicles also exhibited tumor-promoting activity in a mouse model of renal cancer allografts with enhanced angiogenesis. These results suggest that extracellular vesicles released by C. acnes localized in renal cell carcinoma tissues act in a tumor-promoting manner.

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.

Cutibacterium acnes biofilm formation is influenced by bone microenvironment, implant surfaces and bacterial internalization.

BACKGROUND: The bacterial persistence, responsible for therapeutic failures, can arise from the biofilm formation, which possesses a high tolerance to antibiotics. This threat often occurs when a bone and joint infection is diagnosed after a prosthesis implantation. Understanding the biofilm mechanism is pivotal to enhance prosthesis joint infection (PJI) treatment and prevention. However, little is known on the characteristics of Cutibacterium acnes biofilm formation, whereas this species is frequently involved in prosthesis infections. METHODS: In this study, we compared the biofilm formation of C. acnes PJI-related strains and non-PJI-related strains on plastic support and textured titanium alloy by (i) counting adherent and viable bacteria, (ii) confocal scanning electronic microscopy observations after biofilm matrix labeling and (iii) RT-qPCR experiments. RESULTS: We highlighted material- and strain-dependent modifications of C. acnes biofilm. Non-PJI-related strains formed aggregates on both types of support but with different matrix compositions. While the proportion of polysaccharides signal was higher on plastic, the proportions of polysaccharides and proteins signals were more similar on titanium. The changes in biofilm composition for PJI-related strains was less noticeable. For all tested strains, biofilm formation-related genes were more expressed in biofilm formed on plastic that one formed on titanium. Moreover, the impact of C. acnes internalization in osteoblasts prior to biofilm development was also investigated. After internalization, one of the non-PJI-related strains biofilm characteristics were affected: (i) a lower quantity of adhered bacteria (80.3-fold decrease), (ii) an increase of polysaccharides signal in biofilm and (iii) an activation of biofilm gene expressions on textured titanium disk. CONCLUSION: Taken together, these results evidenced the versatility of C. acnes biofilm, depending on the support used, the bone environment and the strain.

Pro-inflammatory activity of Cutibacterium acnes phylotype IA1 and extracellular vesicles: An in vitro study.

Acne is a chronic inflammatory skin condition that involves Cutibacterium acnes (C. acnes), which is classified into six main phylotypes (IA1, IA2, IB, IC, II and III). Acne development is associated with loss of C. acnes phylotype diversity, characterised by overgrowth of phylotype IA1 relative to other phylotypes. It was also shown that purified extracellular vesicles (EVs) secreted by C. acnes can induce an acne-like inflammatory response in skin models. We aimed to determine if the inflammatory profile of EVs secreted by C. acnes phylotype IA1 from an inflammatory acne lesion was different from C. acnes phylotype IA1 from normal skin, thus playing a direct role in the severity of inflammation. EVs were produced in vitro after culture of two clinical strains of C. acnes phylotype IA1, T5 from normal human skin and A47 from an inflammatory acne lesion, and then incubated with either human immortalised keratinocytes, HaCaT cells, or skin explants obtained from abdominoplasty. Subsequently, quantitative PCR (qPCR) was performed for human ß-defensin 2 (hBD2), cathelicidin (LL-37), interleukin (IL)-1ß, IL-6, IL-8, IL-17α and IL-36γ, and ELISA for IL-6, IL-8 and IL-17α. We found that EVs produced in vitro by C. acnes derived from inflammatory acne lesions significantly increased the pro-inflammatory cytokines and anti-microbial peptides at both transcriptional and protein levels compared with EVs derived from normal human skin. We show for the first time that C. acnes EVs from inflammatory acne play a crucial role in acne-associated inflammation in vitro and that C. acnes phylotype IA1 collected from inflammatory acne lesion and normal skin produce different EVs and inflammatory profiles in vitro.

Cutibacterium acnes contamination does not enhance the proinflammatory profile of platelet concentrates.

BACKGROUND: Cutibacterium acnes, a common anaerobic platelet concentrate (PC) contaminant, has been associated with rare mild adverse transfusion reactions and is often considered a harmless commensal. Notably, C. acnes can cause chronic infections and has been shown to induce the release of proinflammatory cytokines by immune cells. Since elevated concentrations of proinflammatory factors in PCs have been linked to noninfectious adverse reactions, this study aimed to assess whether C. acnes could elicit the release and accumulation of proinflammatory factors during PC storage, thereby enhancing the risk of such reactions. STUDY DESIGN/METHODS: Four ABO-matched buffy coat PCs were pooled and split into six units, each were inoculated with either saline (negative control), a Staphylococcus aureus isolate (positive control, 30 colony forming units [CFU]/unit), or four C. acnes PC isolates (10 CFU/mL) and stored at 20-24°C with agitation. Bacterial counts, platelet activation, and concentration of proinflammatory factors were assessed on days 0, 3, and 5. N = 3. RESULTS: C. acnes counts remained stable, while S. aureus proliferated reaching 108CFU/mL by the end of PC storage. By day 5, no significant differences in platelet activation or proinflammatory cytokine profiles were observed in C. acnes-contaminated PCs compared to the negative control (p > .05), while there was a significant increase (p ≤ .05) in sCD40L concentration (day 3), and platelet activation and IL-8 concentration (day 5) in S. aureus-contaminated units. DISCUSSION: C. acnes contamination does not promote the accumulation of proinflammatory factors in the absence of proliferation during storage and may not enhance the risk of inflammatory reactions when transfused to patients.

Analysis of intracellular communication reveals consistent gene changes associated with early-stage acne skin.

A comprehensive understanding of the intricate cellular and molecular changes governing the complex interactions between cells within acne lesions is currently lacking. Herein, we analyzed early papules from six subjects with active acne vulgaris, utilizing single-cell and high-resolution spatial RNA sequencing. We observed significant changes in signaling pathways across seven different cell types when comparing lesional skin samples (LSS) to healthy skin samples (HSS). Using CellChat, we constructed an atlas of signaling pathways for the HSS, identifying key signal distributions and cell-specific genes within individual clusters. Further, our comparative analysis revealed changes in 49 signaling pathways across all cell clusters in the LSS- 4 exhibited decreased activity, whereas 45 were upregulated, suggesting that acne significantly alters cellular dynamics. We identified ten molecules, including GRN, IL-13RA1 and SDC1 that were consistently altered in all donors. Subsequently, we focused on the function of GRN and IL-13RA1 in TREM2 macrophages and keratinocytes as these cells participate in inflammation and hyperkeratinization in the early stages of acne development. We evaluated their function in TREM2 macrophages and the HaCaT cell line. We found that GRN increased the expression of proinflammatory cytokines and chemokines, including IL-18, CCL5, and CXCL2 in TREM2 macrophages. Additionally, the activation of IL-13RA1 by IL-13 in HaCaT cells promoted the dysregulation of genes associated with hyperkeratinization, including KRT17, KRT16, and FLG. These findings suggest that modulating the GRN-SORT1 and IL-13-IL-13RA1 signaling pathways could be a promising approach for developing new acne treatments.

Simultaneous removal of crude oil and heavy metals by highly adapted bacterial strain Cutibacterium sp. NL2 isolated from Algerian oilfield.

Investigating the ability of bacteria to simultaneously enhance hydrocarbon removal and reduce heavy metals' toxicity is necessary to design more effective bioremediation strategies. A bacterium (NL2 strain) isolated from an Algerian oilfield was cultivated on crude oil as sole carbon and energy sources. Molecular analyses of the 16S rRNA gene sequence placed the strain within the Cutibacterium genera. This isolate was able to tolerate up to 60% of crude oil as sole carbon source. Chemical analyses (GC-MS) evidenced that strain NL2 was able to degrade 92.22% of crude oil (at optimal growing conditions: pH 10, 44 °C, 50 g L-1 NaCl, and 20% of crude oil (v/v) as sole carbon source) in only 7 days. NL2 isolate was also able to produce biosurfactants with reduction of surface tension of growing media (29.4 mN m-1). On the other hand, NL2 strain was able to tolerate high lead (Pb) and copper (Cu) concentrations (up to 60 mM). In fact, NL2 cultivated in the presence of 20% of crude oil, and 0.48 mM of Pb was able to reduce Pb concentration by a 41.36%. In turn, when cultivated on high Pb concentration (15 mM), the strain was able to remove 35.19% of it and 86.25% of crude oil, both in a time frame of 7 days. Our findings suggest that Cutibacterium strain NL2 is able to efficiently use and remove a wide range of crude oil substrates in presence of high Pb concentration. Accordingly, NL2 strain is of extreme interest from a biotechnological standpoint.

Cutibacterium namnetense osteosynthetic cervical spine infections: experience with two cases.

We report two uncommon cases of osteosynthetic cervical spine infection. Clinical patient features, microbiological strain characteristics, diagnostic methods, and treatment were analyzed. Both patients were male, and one had risk factors for surgical site infection. During surgery, perioperative samples were positive yielding an anaerobic microorganism identified as Cutibacterium namnetense by MALDI-TOF MS and confirmed by 16S rRNA/gyrB genes sequencing. All isolates were fully susceptible. C. namnetense osteosynthetic cervical spine infections are rare. Both cases were early surgical site infections. Bruker MALDI-TOF MS appears to be an excellent tool for rapid and accurate identification. Amoxicillin seems to be an option for the treatment.

Unusual Cutibacterium acnes splenic abscess with bacteremia in an immunocompetent man: phylotyping and clonal complex analysis.

BACKGROUND: Cutibacterium acnes is an anaerobic bacterium mostly implicated in cutaneous and body-implant infections. Splenic abscess is a rare entity and C. acnes abscesses have only exceptionally been reported. We describe a spontaneous splenic C. acnes abscess in an immunocompetent man with no predisposing factors or identified portal of entry. His isolates were subjected to single-locus sequence typing (SLST) to explore their genetic relatedness and better understand this rare infection. CASE PRESENTATION: A splenic abscess was diagnosed on a computed-tomography scan in a 74-year-old man with chronic abdominal pain. No risk factor was identified. Abscess-drained pus and post-drainage blood cultures grew C. acnes. SLST of abscess and blood isolates showed that they belonged to the same C. acnes SLST type C1 found in normal skin and rarely in inflammatory skin disease. Specific virulence factors could not be identified. CONCLUSION: C. acnes abscesses are extremely rare and can develop in immunocompetent patients without an identifiable portal of entry. Molecular typing of clinical isolates can help confirm infection (versus contamination) and enables genetic background comparisons. Further research is needed to understand C. acnes tropism and virulence.