Cutibacterium acnes

Cutibacterium acnes (Propionibacterium acnes)<ref name="DSMZ">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref name="Scholz">Template:Cite journal</ref><ref name="Dréno">Template:Cite journal</ref><ref name="LPSN">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> is the relatively slow-growing, typically aerotolerant anaerobic, gram-positive bacterium (rod) linked to the skin condition of acne;<ref name="Bhatia2004">Template:Cite book</ref> it can also cause chronic blepharitis and endophthalmitis,<ref name="autogenerated1">Template:Cite journal</ref> the latter particularly following intraocular surgery. Its genome has been sequenced and a study has shown several genes can generate enzymes for degrading skin and proteins that may be immunogenic (activating the immune system).<ref>Template:Cite journal </ref>

The species is largely commensal and part of the skin flora present on most healthy adult humans' skin.<ref>Template:Cite journal</ref> It is usually just barely detectable on the skin of healthy preadolescents. It lives, among other things, primarily on fatty acids in sebum secreted by sebaceous glands in the follicles. It may also be found throughout the gastrointestinal tract.<ref name="expert-reviews2003">Template:Cite journal</ref>

Originally identified as Bacillus acnes,<ref name="Gilchrist">Template:Cite journal</ref> it was later named Propionibacterium acnes for its ability to generate propionic acid.<ref name="Douglas">Template:Cite journal</ref> In 2016, P. acnes was taxonomically reclassified as a result of biochemical and genomic studies. In terms of both phylogenetic tree structure and DNA G + C content, the cutaneous species was distinguishable from other species that had been previously categorized as P. acnes.<ref name="Scholz"/><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> As part of restructuring, the novel genus Cutibacterium was created for the cutaneous species,<ref name="Scholz"/> including those formerly identified as Propionibacterium acnes, Propionibacterium avidum, and Propionibacterium granulosum.<ref name="DSMZ"/> Characterization of phylotypes of C. acnes is an active field of research.<ref name="Dréno"/><ref name="Dagnelie">Template:Cite journal</ref><ref name="Zeller">Template:Cite journal</ref>

Role in diseases

Acne vulgaris

Cutibacterium acnes bacteria predominantly live deep within follicles and pores, although they are also found on the surface of healthy skin.<ref name="Dréno"/> In these follicles, C. acnes bacteria use sebum, cellular debris and metabolic byproducts from the surrounding skin tissue as their primary sources of energy and nutrients. Elevated production of sebum by hyperactive sebaceous glands (sebaceous hyperplasia) or blockage of the follicle can cause C. acnes bacteria to grow and multiply.<ref>Template:Cite journal</ref>

Cutibacterium acnes bacteria secrete many proteins, including several digestive enzymes.<ref>Template:Cite journal</ref> These enzymes are involved in the digestion of sebum and the acquisition of other nutrients. They can also destabilize the layers of cells that form the walls of the follicle. The cellular damage, metabolic byproducts and bacterial debris produced by the rapid growth of C. acnes in follicles can trigger inflammation.<ref>Template:Cite journal</ref> This inflammation can lead to the symptoms associated with some common skin disorders, such as folliculitis and acne vulgaris.<ref>Template:Cite journal</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web

}}</ref> Acne vulgaris is the disease most commonly associated with C. acnes infection.Template:Cn Cutibacterium acnes is one of the most common and universal skin diseases, affecting more than 45 million individuals in the United States. 20% of all dermatologist visits are related to treating acne-related issues. This issue often develops during hormonal periods; however, it is also apparent through early adulthood.<ref name="Bhatia2004"/> There are no quantitative differences between C. acnes of the skin of patients with acne, but the C. acnes phylogenetic groups display distinct genetic and phenotypic characteristics. C. acnes biofilms are also found much more frequently in acne and can induce distinct immune responses to combat against acne. <ref name=":1">Template:Cite journal</ref>

File:Comedo acne 0001.jpg

Comedo acne from C. acnes

Acne vulgaris is a chronic inflammatory disease of the pilosebaceous unit, which includes the hair follicle, hair shaft, and sebaceous gland and about 650 million people are affected globally by this disease.<ref>Template:Cite journal</ref> C. acnes starts to colonize on the skin around 1 to 3 years prior to puberty and grows exponentially during this time.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> This is why so many teens and young adults struggle with acne. Prescriptions to treat acne are often antibiotics. However, with the rise of antibiotic resistance, antibiotics are now often combined with broad-spectrum antibacterial agents such as benzoyl peroxide, and other medications like isotretinoin (commonly known by the brand name Accutane) are being used on patients with severe or resistant acne.<ref>Template:Cite journal</ref>

Staphylococcus epidermidis

The damage caused by C. acnes and the associated inflammation make the affected tissue more susceptible to colonization by opportunistic bacteria, such as Staphylococcus aureus. Preliminary research shows healthy pores are only colonized by C. acnes, while unhealthy ones universally include the nonpore-resident Staphylococcus epidermidis, amongst other bacterial contaminants. Whether this is a root causality, just opportunistic and a side effect, or a more complex pathological duality between C. acnes and this particular Staphylococcus species is not known.<ref name="Propionibacterium acnes DNA detecte">Template:Cite journal</ref> Current research has pointed to the idea that C. acnes and S. epidermidis have a symbiotic relationship.<ref name=":0">Template:Cite journal</ref> Both bacteria exist on the normal flora of the skin and a disrupt in balance of these bacteria on the skin can result in acne or other bacterial infection.<ref name=":0" />

In addition to contributing to skin inflammation and acne lesions, an imbalance in these bacteria may also impair the skin's ability to heal and regenerate, leading to prolonged and more severe acne outbreaks. This disruption can also affect the skin's overall microbiome diversity, potentially increasing susceptibility to other skin conditions such as eczema or rosacea. Investigating the dynamics of this relationship may offer insights into novel therapeutic approaches for managing various skin disorders.<ref>Template:Cite journal</ref>

Ophthalmic complications

Cutibacterium acnes is a common cause of chronic endophthalmitis following cataract surgery. The pathogen may also cause corneal ulcers.<ref>Template:Cite journal</ref>

Disk herniation

Cutibacterium acnes has been found in herniated discs.<ref>Template:Cite journal</ref> The propionic acid which it secretes creates micro-fractures of the surrounding bone. These micro-fractures are sensitive and it has been found that antibiotics have been helpful in resolving this type of low back pain.<ref>Template:Cite journal</ref>

Sarcoidosis

Cutibacterium acnes can be found in bronchoalveolar lavage of approximately 70% of patients with sarcoidosis and is associated with disease activity, but it can also be found in 23% of controls.<ref name="Propionibacterium acnes DNA detecte"/><ref>Template:Cite journal</ref> The subspecies of C. acnes that cause these infections of otherwise sterile tissues (prior to medical procedures), however, are the same subspecies found on the skin of individuals who do not have acne-prone skin, so are likely local contaminants. Moderate to severe acne vulgaris appears to be more often associated with virulent strains.<ref>Template:Cite journal</ref>

Opportunistic diseases

Cutibacterium acnes is often considered an opportunistic pathogen, causing a range of postoperative and device-related infections, notably e.g., surgical infections,<ref>Haidar R., Najjar M., Boghossian A.D., Tabbarah Z., "Propionibacterium acnes causing delayed postoperative spine infection: Review." Scandinavian Journal of Infectious Diseases. 42 (6-7) (pp 405-411), 2010</ref> post-neurosurgical infections,<ref>Nisbet, M.; Briggs, S.; Ellis-Pegler, R.; Thomas, M. ;Holland, D. "Propionibacterium acnes: an under-appreciated cause of post-neurosurgical infection" Journal of Antimicrobial Chemotherapy. 60(5). NOV 2007. 1097-1103.1103.</ref> infected joint prostheses (especially shoulder),<ref>Template:Cite journal</ref> neurosurgical shunt infections and endocarditis in patients with prosthetic heart valves (predominantly men).<ref>Template:Cite journal</ref> C. acnes may play a role in other conditions, including SAPHO (synovitis, acne, pustulosis, hyperostosis, osteitis) syndrome, sarcoidosis and sciatica.<ref>Perry A., Lambert P. " Propionibacterium acnes: Infection beyond the skin." Expert Review of Anti-Infective Therapy. 9 (12) (pp 1149-1156), 2011</ref> It is also suspected a main bacterial source of neuroinflammation in Alzheimer's disease brains.<ref>Template:Cite journal</ref> It is a common contaminant in blood and cerebrospinal fluid cultures.<ref name="Portillo">Template:Cite journal</ref><ref name="Gharamti">Template:Cite journal</ref>

Antimicrobial susceptibility

Cutibacterium acnes bacteria are susceptible to a wide range of antimicrobial molecules, from both pharmaceutical and natural sources. The antibiotics most frequently used to treat acne vulgaris are erythromycin, clindamycin, doxycycline, and minocycline.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref>Template:Cite journal</ref> Several other families of antibiotics are also active against C. acnes bacteria, including quinolones, cephalosporins, pleuromutilins, penicillins, and sulfonamides.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Antibiotic-resistance

The emergence of antibiotic-resistant C. acnes bacteria represents a growing problem worldwide.<ref>Template:Cite journal</ref> The problem is especially pronounced in North America and Europe.<ref>Template:Cite journal</ref> The antibiotic families that C. acnes are most likely to acquire resistance to are the macrolides (e.g., erythromycin and azithromycin), lincosamides (e.g., clindamycin) and tetracyclines (e.g., doxycycline and minocycline).<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref>

However, C. acnes bacteria are susceptible to many types of antimicrobial chemicals found in over-the-counter antibacterial products, including benzoyl peroxide,<ref>Template:Cite journal</ref> triclosan,<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> chloroxylenol,<ref name="Emsley">Template:Cite book</ref> and chlorhexidine gluconate.<ref name="Shimizu">Template:Cite journal</ref>

C. acnes resistance to antibiotics has increased to 64% in 2000, up from 20% in 1979. Treatments such as oral macrolides are often avoided because the bacteria has become resistant in most cases. This creates a public health issue, forcing healthcare providers to seek out other forms of treatment.<ref name=":1" />

Treatments

Several naturally occurring molecules and compounds are toxic to C. acnes bacteria. Some essential oils such as rosemary,<ref name="pmid17893831">Template:Cite journal</ref> tea tree oil,<ref>Template:Cite journal</ref> clove oil,<ref>Template:Cite journal</ref> and citrus oils<ref>Template:Cite journal</ref><ref name="pmid18239420">Template:Cite journal</ref> contain antibacterial chemicals. Natural honey has also been shown to have some antibacterial properties that may be active against C. acnes.<ref>Template:Cite journal</ref>

The elements silver,<ref>Template:Cite journal</ref> sulfur,<ref>Template:Cite journal</ref> and copper<ref>Template:Cite journal</ref> have also been demonstrated to be toxic towards many bacteria, including C. acnes.

Salicylic acid is a naturally occurring substance derived from plants (white willow bark and wintergreen leaves) used to promote exfoliation of the skin in order to treat acne. Additionally, research investigates the mechanism by which salicylic acid (SA) treats acne vulgaris. A study finds that SA suppresses the AMPK/SREBP1 (AMP-activated protein kinase)(AMPK/SREBP1 pathway is a signaling pathway involved in the regulation of lipid metabolism in sebocytes, which are the cells responsible for producing sebum in the skin) pathway in sebocytes, leading to a decrease in lipid synthesis and sebum production. SA also reduces the inflammatory response of sebocytes and decreases the proliferation of C. acnes. These results suggest that SA has a multifaceted approach in treating acne vulgaris by targeting several key factors that contribute to its development.<ref>Template:Cite journal</ref> The minimum inhibitory concentration for SA is 4000–8000 μg/mL.<ref>Template:Cite journal</ref>

Photosensitivity

Cutibacterium acnes glows orange when exposed to blacklight, possibly due to the presence of endogenous porphyrins. It is also killed by ultraviolet light. C. acnes is especially sensitive to light in the 405–420 nanometer (near the ultraviolet) range due to an endogenic porphyrin–coporphyrin III. A total radiant exposure of 320 J/cm² inactivates this species in vitro.<ref name="british">Template:Cite journal</ref> Its photosensitivity can be enhanced by pretreatment with aminolevulinic acid, which boosts production of this chemical, although this causes significant side effects in humans, and in practice was not significantly better than the light treatment alone.<ref name="Togsverd-Bo">Template:Cite journal</ref><ref name="Lin">Template:Cite journal</ref>

Other habitats

Cutibacterium acnes has been found to be an endophyte of plants. Notably, grapevine appears to host an endophytic population of C. acnes that is closely related to the human-associated strains. The two lines diverged roughly 7,000 years ago, at about the same time when grapevine agriculture may have been established. This C. acnes subtype was dubbed Zappae in honour of the eccentric composer Frank Zappa, to highlight its unexpected and unconventional habitat.<ref name="zappa">Template:Cite journal</ref>

External links

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• Propionibacterium (Kenyon College)
• Type strain of Propionibacterium acnes at BacDive - the Bacterial Diversity Metadatabase