The anaerobic bacterium Cutibacterium acnes has been increasingly linked to the development of degenerative disc disease (DDD), although causality is yet to be conclusively proven. To better study how this organism could contribute to the aetiology of DDD, improved animal models that are more reflective of human disc anatomy, biology and mechanical properties are required. Against this background, our proof-of concept study aimed to be the first demonstration that C. acnes could be safely administered percutaneously into sheep intervertebral discs (IVDs) for in vivo study. Following our protocol, two sheep were successfully injected with a strain of C. acnes (8.3 × 106 CFU/disc) previously recovered from a human degenerative disc. No adverse reactions were noted, and at one-month post inoculation all triplicate infected discs in our first animal grew C. acnes, albeit at a reduced load (5.12 × 104 to 6.67 × 104 CFU/disc). At six months, no growth was detected in discs from our second animal indicating bacterial clearance. This pilot study has demonstrated the feasibility of safe percutaneous injection of C. acnes into sheep IVDs under fluoroscopic guidance. The design of follow-up sheep studies to investigate the potential of C. acnes to drive pathological changes within infected discs should now be pursued.

• Keywords
• Cutibacterium acnes, bacterial discitis, percutaneous injections, sheep model, spinal intervertebral discs,
• Publication type
• Journal Article MeSH

Previously, we proposed the hypothesis that similarities in the inflammatory response observed in acne vulgaris and degenerative disc disease (DDD), especially the central role of interleukin (IL)-1β, may be further evidence of the role of the anaerobic bacterium Cutibacterium (previously Propionibacterium) acnes in the underlying aetiology of disc degeneration. To investigate this, we examined the upregulation of IL-1β, and other known IL-1β-induced inflammatory markers and neurotrophic factors, from nucleus-pulposus-derived disc cells infected in vitro with C. acnes for up to 48 h. Upon infection, significant upregulation of IL-1β, alongside IL-6, IL-8, chemokine (C-C motif) ligand 3 (CCL3), chemokine (C-C motif) ligand 4 (CCL4), nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), was observed with cells isolated from the degenerative discs of eight patients versus non-infected controls. Expression levels did, however, depend on gene target, multiplicity and period of infection and, notably, donor response. Pre-treatment of cells with clindamycin prior to infection significantly reduced the production of pro-inflammatory mediators. This study confirms that C. acnes can stimulate the expression of IL-1β and other host molecules previously associated with pathological changes in disc tissue, including neo-innervation. While still controversial, the role of C. acnes in DDD remains biologically credible, and its ability to cause disease likely reflects a combination of factors, particularly individualised response to infection.

• Keywords
• Cutibacterium acnes, co-culture, disc cells, gene expression, inflammation, intracellular, neurotrophic factors,
• MeSH
• Intervertebral Disc Degeneration genetics   microbiology   MeSH
• Adult MeSH
• Host-Pathogen Interactions MeSH
• Interleukin-1beta genetics   MeSH
• Cells, Cultured MeSH
• Middle Aged MeSH
• Humans MeSH
• Intervertebral Disc metabolism   microbiology   MeSH
• Nerve Growth Factors genetics   MeSH
• Propionibacterium acnes physiology   MeSH
• Up-Regulation MeSH
• Inflammation genetics   microbiology   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Interleukin-1beta MeSH
• Nerve Growth Factors MeSH

• MeSH
• Bacteria MeSH
• Leg * MeSH
• Back Pain MeSH
• Humans MeSH
• Intervertebral Disc Displacement * MeSH
• Check Tag
• Humans MeSH
• Publication type
• Letter MeSH
• Comment MeSH

PURPOSE: Recent research shows an increasing recognition that organisms not traditionally considered infectious in nature contribute to disease processes. Propionibacterium acnes (P. acnes) is a gram-positive, aerotolerant anaerobe prevalent in the sebaceous gland-rich areas of the human skin. A ubiquitous slow-growing organism with the capacity to form biofilm, P. acnes, recognized for its role in acne vulgaris and medical device-related infections, is now also linked to a number of other human diseases. While bacterial culture and molecular techniques are used to investigate the involvement of P. acnes in such diseases, definitive demonstration of P. acnes infection requires a technique (or techniques) sensitive to the presence of biofilms and insensitive to the presence of potential contamination. Fortunately, there are imaging techniques meeting these criteria, in particular, fluorescence in situ hybridization and immunofluorescence coupled with confocal laser scanning microscopy, as well as immunohistochemistry. METHODS: Our literature review considers a range of microscopy-based studies that provides definitive evidence of P. acnes colonization within tissue from a number of human diseases (acne vulgaris, degenerative disc and prostate disease and atherosclerosis), some of which are currently not considered to have an infectious etiology. RESULTS/CONCLUSION: We conclude that P. acnes is an opportunistic pathogen with a likely underestimated role in the development of various human diseases associated with significant morbidity and, in some cases, mortality. As such, these findings offer the potential for new studies aimed at understanding the pathological mechanisms driving the observed disease associations, as well as novel diagnostic strategies and treatment strategies, particularly for degenerative disc disease. These slides can be retrieved under Electronic Supplementary Material.

• Keywords
• Acne vulgaris, Arthroscopy, Atherosclerosis, Biofilm, Cutibacterium acnes, Degenerative disc disease, FISH-CLSM, Propionibacterium acnes, Prostate cancer,
• MeSH
• Acne Vulgaris diagnostic imaging   microbiology   MeSH
• Biofilms * MeSH
• Intervertebral Disc Degeneration * diagnostic imaging   microbiology   MeSH
• Gram-Positive Bacterial Infections * diagnostic imaging   microbiology   MeSH
• Humans MeSH
• Microscopy * MeSH
• Propionibacterium acnes * MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

• MeSH
• Bacterial Infections * MeSH
• Diskectomy MeSH
• Humans MeSH
• Intervertebral Disc * MeSH
• Prospective Studies MeSH
• Virulence MeSH
• Check Tag
• Humans MeSH
• Publication type
• Letter MeSH
• Comment MeSH

PURPOSE: The presence of Propionibacterium acnes in a substantial component of resected disc specimens obtained from patients undergoing discectomy or microdiscectomy has led to the suggestion that this prominent human skin and oral commensal may exacerbate the pathology of degenerative disc disease. This hypothesis, therefore, raises the exciting possibility that antibiotics could play an important role in treating this debilitating condition. To date, however, little information about antibiotic penetration into the intervertebral disc is available. METHODS: Intervertebral disc tissue obtained from 54 microdiscectomy patients given prophylactic cefazolin (n = 25), clindamycin (n = 17) or vancomycin (n = 12) was assayed by high-performance liquid chromatography, with cefaclor as an internal standard, to determine the concentration of antibiotic penetrating into the disc tissue. RESULTS: Intervertebral disc tissues from patients receiving the positively charged antibiotic clindamycin contained a significantly greater percentage of the antibacterial dose than the tissue from patients receiving negatively charged cefazolin (P < 0.0001) and vancomycin, which has a slight positive charge (P < 0.0001). CONCLUSION: Positively charged antibiotics appear more appropriate for future studies investigating potential options for the treatment of low-virulence disc infections. These slides can be retrieved under Electronic Supplementary Material.

• Keywords
• Biofilm, Cefazolin, Clindamycin, Cutibacterium acnes, Degenerative disc disease, Propionibacterium acnes, Surgical prophylaxis, Vancomycin,
• MeSH
• Anti-Bacterial Agents pharmacokinetics   therapeutic use   MeSH
• Cefazolin pharmacokinetics   therapeutic use   MeSH
• Intervertebral Disc Degeneration surgery   MeSH
• Adult MeSH
• Gram-Positive Bacterial Infections prevention & control   MeSH
• Clindamycin pharmacokinetics   therapeutic use   MeSH
• Humans MeSH
• Intervertebral Disc metabolism   MeSH
• Propionibacterium acnes * MeSH
• Vancomycin pharmacokinetics   therapeutic use   MeSH
• Intervertebral Disc Displacement surgery   MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Anti-Bacterial Agents MeSH
• Cefazolin MeSH
• Clindamycin MeSH
• Vancomycin MeSH

Most patients with chronic lower back pain (CLBP) exhibit degenerative disc disease. Disc specimens obtained during initial therapeutic discectomies are often infected/colonized with Propionibacterium acnes, a Gram-positive commensal of the human skin. Although pain associated with infection is typically ascribed to the body's inflammatory response, the Gram-positive bacterium Staphylococcus aureus was recently observed to directly activate nociceptors by secreting pore-forming α-hemolysins that disrupt neuronal cell membranes. The hemolytic activity of P. acnes in cultured disc specimens obtained during routine therapeutic discectomies was assessed through incubation on sheep-blood agar. The β-hemolysis pattern displayed by P. acnes on sheep-blood agar was variable and phylogroup-dependent. Their molecular phylogroups were correlated with their hemolytic patterns. Our findings raise the possibility that pore-forming proteins contribute to the pathogenesis and/or symptomology of chronic P. acnes disc infections and CLBP, at least in a subset of cases.

• MeSH
• Chronic Disease MeSH
• Gram-Positive Bacterial Infections complications   microbiology   pathology   MeSH
• Hemolysis * MeSH
• Humans MeSH
• Low Back Pain complications   microbiology   pathology   MeSH
• Intervertebral Disc microbiology   pathology   MeSH
• Sheep MeSH
• Propionibacterium acnes physiology   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

The pathogenesis of degenerative disc disease is a complex and multifactorial process in which genetics, mechanical trauma, altered loading and nutrition present significant etiological factors. Infection of the intervertebral disc with the anaerobic bacterium Propionibacterium acnes is now also emerging as a potentially new etiological factor. This human commensal bacterium is well known for its long association with the inflammatory skin condition acne vulgaris. A key component of inflammatory responses to P. acnes in acne appears to be interleukin (IL)-1β. Similarly, in degenerative disc disease (DDD) there is compelling evidence for the fundamental roles of IL-1β in its pathology. We therefore propose that P. acnes involvement in DDD is biologically very plausible, and that IL-1β is the key inflammatory mechanism driving the host response to P. acnes infection. Since there is a solid theoretical basis for this phenomenon, we further propose that the relationship between P. acnes infection and DDD is causal.

• Keywords
• Propionibacterium acnes, acne vulgaris, degenerative disc disease, interleukin-1 beta, nerve growth factor (NGF),
• MeSH
• Models, Biological MeSH
• Intervertebral Disc Degeneration etiology   physiopathology   MeSH
• Discitis complications   microbiology   MeSH
• Gram-Positive Bacterial Infections complications   microbiology   MeSH
• Interleukin-1beta metabolism   MeSH
• Humans MeSH
• Propionibacterium acnes growth & development   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Interleukin-1beta MeSH