# _Cutibacterium acnes_ Dysbiosis: Alternative Therapeutics for Clinical Application
### C. acnes Infection and Virulence Factors  
_Cutibacterium acnes_, or _C. acnes_, was firstly isolated from a patient with chronic acne vulgaris (AV) in the 1900s. It constitutes a healthy human commensal, Gram-positive, and anaerobic facultative bacterium [3]. _C. acnes_ has a broad distribution on the human body, including face, supra, subgingival plaque, back, chest, groin, bend of elbow, intestine, inguinal canal, forearm, palm, plantar heel, and toe, as part of the skin's microbiota [2,4]. Under normal circumstances, _C. acnes_ does not cause harm and coexists peacefully with other microorganisms. In some situations, however, there can be an overgrowth that can occur when factors like excess sebum production, hormonal changes, or inflammation create conditions favorable for bacterial proliferation. This proliferation permits the formation of biofilms that allow the bacterium to adhere to surfaces, including hair follicles and sebaceous glands on the skin. These biofilms constitute one of several virulence factors that bacteria possess as part of their defense mechanism (Figure 1) [3].  
Figure 1: _C. acnes_ virulence factors allow the bacteria to cause an infection and to survive the host defenses. There are several mechanisms in _C. acnes_ to promote the infection, the evasion of the host defenses, host tissue damage, and invasion, such as a—Lipases can break down sebum and release the free fatty acids, influencing the bacterial capacity to adhere to other cells and surfaces which leads to the formation of comedones; b—Polyunsaturated Fatty Acid Isomerase promotes the catalyzation and the isomerization of linoleic acid; c—Reactive oxygen species (ROS) produced by macrophages (c1) are reduced by _C. acnes_’ radical oxygenase, inactivating its deadly effects (c2); d—Bacterial biofilms consist of an extracellular matrix composed of proteins, polysaccharides, and/or extracellular DNA. Biofilm production protects _C. acnes_ against the host immune system, most likely by creating a barrier that protects the bacteria from harmful environments such as antibiotics; e—Christ–Atkins–Much–Petersen Factors (CAMP factors) produced by _C. acnes_ (e1) lead to tissue damage by creating membrane pores that promote the lysis of the host cells (e2); f—Hyaluronate lyase promotes the degradation of the hostepidermis and dermis extracellular matrix components, such as glycosaminoglycans and hyaluronic acid, allowing the bacterial invasion in the host tissues by the degradation of the skin layers and dissemination of the inflammation; g--Glycosidase enzymes break carbohydrate structures such as host glycolipids and glycoproteins, which permits _C. acnes_ to use host carbohydrates to grow; h--C. acnes' DsA1 binds to the dermatan sulfate and to fibrinogen protein, involved in the biofilm formation; j--Salidases remove sialic acid within sialoglyco conjugates, a highly immunogenic protein, although their function in the bacteria pathogenicity is still not clear; l--Sortases F permit the attachment to different proteins, like adhesion factors. These en-zymes are produced in the cytoplasm and promote the transportation of proteins to the bacterial wall.  
The virulence ability comprises several molecular mechanisms that microorganisms use to infect the host cells and tissues. These virulence factors, summarized in Table 1, are associated with bacterial adhesion and tissue invasion/degradation of the host tissues, allowing the microorganism to overrun the host's immune system and antibiotic treatments [3].  
It is important to note that not all individuals carrying _C. acnes_ will develop this pathogenicity. The transition from commensal to pathogenic depends on various factors, including host genetics, the local microenvironment, and the immune response. The mechanisms underlying these transitions are complex and are an active area of research in dermatology, immunology, and microbiology.