Cutibacterium acnes

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Cutibacterium acnes
Propionibacterium acnes.jpg
Scientific classification OOjs UI icon edit-ltr.svg
Domain: Bacteria
Phylum: Actinomycetota
Class: Actinomycetia
Order: Propionibacteriales
Family: Propionibacteriaceae
Genus: Cutibacterium
Species:
C. acnes
Binomial name
Cutibacterium acnes
Scholz and Kilian, 2016 [1] [2]
Subspecies
Synonyms
  • "Bacillus acnes" Gilchrist 1900
  • Propionibacterium acnes(Gilchrist 1900) Douglas and Gunter 1946 (Approved Lists 1980)

Cutibacterium acnes (Propionibacterium acnes) [1] [2] [3] [4] is the relatively slow-growing, typically aerotolerant anaerobic, gram-positive bacterium (rod) linked to the skin condition of acne; [5] it can also cause chronic blepharitis and endophthalmitis, [6] 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). [7]

Contents

The species is largely commensal and part of the skin flora present on most healthy adult humans' skin. [8] 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. [9]

Originally identified as Bacillus acnes, [10] it was later named Propionibacterium acnes for its ability to generate propionic acid. [11] 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. [2] [12] As part of restructuring, the novel genus Cutibacterium was created for the cutaneous species, [2] including those formerly identified as Propionibacterium acnes, Propionibacterium avidum , and Propionibacterium granulosum . [1] Characterization of phylotypes of C. acnes is an active field of research. [3] [13] [14]

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. [3] 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. [15]

Cutibacterium acnes bacteria secrete many proteins, including several digestive enzymes. [16] 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. [17] This inflammation can lead to the symptoms associated with some common skin disorders, such as folliculitis and acne vulgaris. [18] [19] Acne vulgaris is the disease most commonly associated with C. acnes infection.[ citation needed ] 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. [5] 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. [20]

Comedo acne from C. acnes 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. [21] C. acnes starts to colonize on the skin around 1 to 3 years prior to puberty and grows exponentially during this time. [22] 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. [23]

Staphylococcusepidermidis

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. [24] Current research has pointed to the idea that C. acnes and S. epidermidis have a symbiotic relationship. [25] 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. [25]

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. [26]

Ophthalmic complications

Cutibacterium acnes is a common cause of chronic endophthalmitis following cataract surgery. The pathogen may also cause corneal ulcers. [27]

Disk herniation

Cutibacterium acnes has been found in herniated discs. [28] 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. [29]

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. [24] [30] 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. [31]

Opportunistic diseases

Cutibacterium acnes is often considered an opportunistic pathogen, causing a range of postoperative and device-related infections, notably e.g., surgical infections, [32] post-neurosurgical infections, [33] infected joint prostheses (especially shoulder), [34] neurosurgical shunt infections and endocarditis in patients with prosthetic heart valves (predominantly men). [35] C. acnes may play a role in other conditions, including SAPHO (synovitis, acne, pustulosis, hyperostosis, osteitis) syndrome, sarcoidosis and sciatica. [36] It is also suspected a main bacterial source of neuroinflammation in Alzheimer's disease brains. [37] It is a common contaminant in blood and cerebrospinal fluid cultures. [38] [39]

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. [40] [41] [42] Several other families of antibiotics are also active against C. acnes bacteria, including quinolones, cephalosporins, pleuromutilins, penicillins, and sulfonamides. [43] [44] [45]

Antibiotic-resistance

The emergence of antibiotic-resistant C. acnes bacteria represents a growing problem worldwide. [46] The problem is especially pronounced in North America and Europe. [47] 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). [48] [49]

However, C. acnes bacteria are susceptible to many types of antimicrobial chemicals found in over-the-counter antibacterial products, including benzoyl peroxide, [50] triclosan, [51] chloroxylenol, [52] and chlorhexidine gluconate. [53]

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. [20]

Treatments

Several naturally occurring molecules and compounds are toxic to C. acnes bacteria. Some essential oils such as rosemary, [54] tea tree oil, [55] clove oil, [56] and citrus oils [57] [58] contain antibacterial chemicals. Natural honey has also been shown to have some antibacterial properties that may be active against C. acnes. [59]

The elements silver, [60] sulfur, [61] and copper [62] 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. [63] The minimum inhibitory concentration for SA is 4000–8000 μg/mL. [64]

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. [65] 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. [66] [67]

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. [68]

Related Research Articles

<span class="mw-page-title-main">Acne</span> Skin condition characterized by pimples

Acne also known as acne vulgaris, is a long-term skin condition that occurs when dead skin cells and oil from the skin clog hair follicles. Typical features of the condition include blackheads or whiteheads, pimples, oily skin, and possible scarring. It primarily affects skin with a relatively high number of oil glands, including the face, upper part of the chest, and back. The resulting appearance can lead to lack of confidence, anxiety, reduced self-esteem, and, in extreme cases, depression or thoughts of suicide.

<span class="mw-page-title-main">Minocycline</span> Antibiotic medication

Minocycline, sold under the brand name Minocin among others, is a tetracycline antibiotic medication used to treat a number of bacterial infections such as some occurring in certain forms of pneumonia. It is generally less preferred than the tetracycline doxycycline. Minocycline is also used for the treatment of acne and rheumatoid arthritis. It is taken by mouth or applied to the skin.

<span class="mw-page-title-main">Dandruff</span> Skin condition of the scalp

Dandruff is a skin condition that mainly affects the scalp. Symptoms include flaking and sometimes mild itchiness. It can result in social or self-esteem problems. A more severe form of the condition, which includes inflammation of the skin, is known as seborrhoeic dermatitis.

<span class="mw-page-title-main">Sebaceous gland</span> Gland to lubricate the hair and skin

A sebaceous gland or oil gland is a microscopic exocrine gland in the skin that opens into a hair follicle to secrete an oily or waxy matter, called sebum, which lubricates the hair and skin of mammals. In humans, sebaceous glands occur in the greatest number on the face and scalp, but also on all parts of the skin except the palms of the hands and soles of the feet. In the eyelids, meibomian glands, also called tarsal glands, are a type of sebaceous gland that secrete a special type of sebum into tears. Surrounding the female nipples, areolar glands are specialized sebaceous glands for lubricating the nipples. Fordyce spots are benign, visible, sebaceous glands found usually on the lips, gums and inner cheeks, and genitals.

<span class="mw-page-title-main">Broad-spectrum antibiotic</span> Treatment for a wide range of bacteria

A broad-spectrum antibiotic is an antibiotic that acts on the two major bacterial groups, Gram-positive and Gram-negative, or any antibiotic that acts against a wide range of disease-causing bacteria. These medications are used when a bacterial infection is suspected but the group of bacteria is unknown or when infection with multiple groups of bacteria is suspected. This is in contrast to a narrow-spectrum antibiotic, which is effective against only a specific group of bacteria. Although powerful, broad-spectrum antibiotics pose specific risks, particularly the disruption of native, normal bacteria and the development of antimicrobial resistance. An example of a commonly used broad-spectrum antibiotic is ampicillin.

<span class="mw-page-title-main">Doxycycline</span> Tetracycline-class antibiotic

Doxycycline is a broad-spectrum antibiotic of the tetracycline class used in the treatment of infections caused by bacteria and certain parasites. It is used to treat bacterial pneumonia, acne, chlamydia infections, Lyme disease, cholera, typhus, and syphilis. It is also used to prevent malaria. Doxycycline may be taken by mouth or by injection into a vein.

Hyperkeratinization is a disorder of the cells lining the inside of a hair follicle. It is the normal function of these cells to detach or slough off from the skin lining at normal intervals. The dead cells are then forced out of the follicle. However, in hyperkeratinization, this process is interrupted and a number of these dead skin cells do not leave the follicle because of an excess of keratin, a natural protein found in the skin. This excess of keratin, which is influenced by genetics, results in an increased adherence/bonding of dead skin cells together. This cohesion of cells will block or "cap" the hair follicle or clog the sebaceous/oil duct. Pathogens may also play a role in causing, perpetuating, or simply taking advantage of this phenomenon, such as virulent sub-strains of Cutibacterium acnes and irregular migration of Staphylococcus epidermidis from the outer surface of the skin into the follicle, where commensal strains of C. acnes exclusively habitate. It itches mildly at times, and strongly at others. Very often it cannot be felt at all.

<span class="mw-page-title-main">Fusidic acid</span> Antibiotic

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<i>Propionibacterium</i> Genus of bacteria

Propionibacterium is a gram-positive, anaerobic, rod-shaped genus of bacteria named for their unique metabolism: They are able to synthesize propionic acid by using unusual transcarboxylase enzymes.

<span class="mw-page-title-main">Comedo</span> Medical condition

A comedo is a clogged hair follicle (pore) in the skin. Keratin combines with oil to block the follicle. A comedo can be open (blackhead) or closed by skin (whitehead) and occur with or without acne. The word "comedo" comes from the Latin comedere, meaning "to eat up", and was historically used to describe parasitic worms; in modern medical terminology, it is used to suggest the worm-like appearance of the expressed material.

<i>Staphylococcus epidermidis</i> Species of bacterium

Staphylococcus epidermidis is a Gram-positive bacterium, and one of over 40 species belonging to the genus Staphylococcus. It is part of the normal human microbiota, typically the skin microbiota, and less commonly the mucosal microbiota and also found in marine sponges. It is a facultative anaerobic bacteria. Although S. epidermidis is not usually pathogenic, patients with compromised immune systems are at risk of developing infection. These infections are generally hospital-acquired. S. epidermidis is a particular concern for people with catheters or other surgical implants because it is known to form biofilms that grow on these devices. Being part of the normal skin microbiota, S. epidermidis is a frequent contaminant of specimens sent to the diagnostic laboratory.

Erythromycin/isotretinoin is a topical gel with two active ingredients: erythromycin 2% w/w and isotretinoin 0.05% w/w with a primary indication for the treatment of moderate acne vulgaris.

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<span class="mw-page-title-main">Skin flora</span> Microbiota that reside on the skin

Skin flora, also called skin microbiota, refers to microbiota that reside on the skin, typically human skin.

<span class="mw-page-title-main">Nadifloxacin</span> Chemical compound

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<span class="mw-page-title-main">Pimple</span> Type of comedo

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<span class="mw-page-title-main">Antibiotic misuse</span> Improper use of antibiotic medications

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Infantile acne is a form of acne that begins in very young children. Typical symptoms include inflammatory and noninflammatory lesions, papules and pustules most commonly present on the face. No cause of infantile acne has been established but it may be caused by increased sebaceous gland secretions due to elevated androgens, genetics and the fetal adrenal gland causing increased sebum production. Infantile acne can resolve by itself by age 1 or 2. However, treatment options include topical benzyl peroxide, topical retinoids and topical antibiotics in most cases.

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