scholarly journals Activation of Deoxyribonuclease I by Nicotinamide as a New Strategy to Attenuate Tetracycline-Resistant Biofilms of Cutibacterium acnes

Pharmaceutics ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 819
Author(s):  
Yi-Hsien Shih ◽  
Donald Liu ◽  
Yen-Chou Chen ◽  
Ming-Hsuan Liao ◽  
Woan-Ruoh Lee ◽  
...  
Keyword(s):  
Acne Vulgaris ◽  
Topical Administration ◽  
Dnase I ◽  
Adjunctive Treatment ◽  
Kinetic Assay ◽  
Surface Plasmon Resonance Analysis ◽  
Cutaneous Infections ◽  
Cutibacterium Acnes

Biofilms of Cutibacterium (C.) acnes (formerly Propionibacterium acnes) are responsible for the persistence and antibiotic resistance of acne vulgaris. In addition to the standard treatments for acne vulgaris, a common adjunctive treatment is the topical administration of nicotinamide (NAM). However, the effects of NAM on biofilms of C. acnes have never been explored. This study comprehensively investigates the effects of NAM against biofilms of C. acnes using in vitro and in vivo approaches. The results showed that NAM potentiated the efficacy of suboptimal dosing of tetracycline against C. acnes. Moreover, NAM alone decreased the formation and increased the degradation of biofilms in C. acnes. The antibiofilm effect of NAM against C. acnes was further enhanced in combination with deoxyribonuclease (DNase) I, an enzyme with known antibiofilm properties. The computational molecular docking, surface plasmon resonance analysis, and enzymatic kinetic assay demonstrated that NAM binds to DNase I and accelerated its reaction. In conclusion, NAM activates DNase I to attenuate biofilms of C. acnes. This offers valuable insights into the strategies against biofilms that are worth elaborating on in other biofilm-related chronic cutaneous infections in the future.

scholarly journals Characterization of Weissella viridescens UCO-SMC3 as a Potential Probiotic for the Skin: Its Beneficial Role in the Pathogenesis of Acne Vulgaris

2021 ◽  
Vol 9 (7) ◽  
pp. 1486
Author(s):  
Marcela Espinoza-Monje ◽  
Jorge Campos ◽  
Eduardo Alvarez Villamil ◽  
Alonso Jerez ◽  
Stefania Dentice Maidana ◽  
...  
Keyword(s):  
Immune Response ◽  
Oral Treatment ◽  
Acne Vulgaris ◽  
Topical Administration ◽  
In Vivo Studies ◽  
Mice Model ◽  
Cutibacterium Acnes ◽  
Snail Helix Aspersa

Previously, we isolated lactic acid bacteria from the slime of the garden snail Helix aspersa Müller and selected Weissella viridescens UCO-SMC3 because of its ability to inhibit in vitro the growth of the skin-associated pathogen Cutibacterium acnes. The present study aimed to characterize the antimicrobial and immunomodulatory properties of W. viridescens UCO-SMC3 and to demonstrate its beneficial effect in the treatment of acne vulgaris. Our in vitro studies showed that the UCO-SMC3 strain resists adverse gastrointestinal conditions, inhibits the growth of clinical isolates of C. acnes, and reduces the adhesion of the pathogen to keratinocytes. Furthermore, in vivo studies in a mice model of C. acnes infection demonstrated that W. viridescens UCO-SMC3 beneficially modulates the immune response against the skin pathogen. Both the oral and topical administration of the UCO-SCM3 strain was capable of reducing the replication of C. acnes in skin lesions and beneficially modulating the inflammatory response. Of note, orally administered W. viridescens UCO-SMC3 induced more remarkable changes in the immune response to C. acnes than the topical treatment. However, the topical administration of W. viridescens UCO-SMC3 was more efficient than the oral treatment to reduce pathogen bacterial loads in the skin, and effects probably related to its ability to inhibit and antagonize the adhesion of C. acnes. Furthermore, a pilot study in acne volunteers demonstrated the capacity of a facial cream containing the UCO-SMC3 strain to reduce acne lesions. The results presented here encourage further mechanistic and clinical investigations to characterize W. viridescens UCO-SMC3 as a probiotic for acne vulgaris treatment.

scholarly journals Inhibitory Effects of a Sargassum miyabei Yendo on Cutibacterium acnes-Induced Skin Inflammation

Nutrients ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2620
Author(s):  
Mi-Jin Yim ◽  
Jeong Min Lee ◽  
Hyun-Soo Kim ◽  
Grace Choi ◽  
Young-Mog Kim ◽  
...  
Keyword(s):  
Acne Vulgaris ◽  
Skin Lesions ◽  
Enzyme Linked Immunosorbent Assay ◽  
Hacat Cells ◽  
Chronic Inflammatory Condition ◽  
Cutibacterium Acnes ◽  
Anti Inflammatory ◽  
Sargassum Miyabei

Acne vulgaris is a chronic inflammatory condition of skin sebaceous follicles. To explore its effects on acne vulgaris, we investigated the antibacterial and anti-inflammatory activities of Sargassum miyabei Yendo (a brown alga) ethanolic extract (SMYEE) on Cutibacterium acnes (C. acnes)-stimulated inflammatory responses, both in vivo and in vitro. To induce inflammation in vivo, C. acnes was intradermally injected into the dorsal skin of mice, to which SMYEE was applied. The antimicrobial activity of SMYEE was evaluated by the determination of minimum inhibitory concentrations (MICs). To explore in vitro anti-inflammatory effects, HaCaT cells were stimulated with C. acnes after treatment with SMYEE. The levels of IL-8 and the underlying molecular effects in C. acnes-stimulated HaCaT cells were assessed by enzyme-linked immunosorbent assay, Western blotting, and an electrophoretic mobility shift assay. Mouse skin lesions improved after treatment with SMYEE (50 μg/mouse). Neutrophil infiltration was significantly reduced in SMYEE-treated compared to SMYEE-untreated skin lesions. SMYEE reversed the C. acnes-induced increase in IL-8 levels in HaCaT cells and suppressed dHL-60 cell migration. SMYEE also inhibited C. acnes-induced phosphorylation of the extracellular signal-regulated kinase and inhibited activator protein-1 signaling. SMYEE may be a useful treatment for C. acnes-induced acne vulgaris.

scholarly journals Propionibacterium (Cutibacterium) granulosum Extracellular DNase BmdE Targeting Propionibacterium (Cutibacterium) acnes Biofilm Matrix, a Novel Inter-Species Competition Mechanism

2022 ◽  
Vol 11 ◽  
Author(s):  
Vicky Bronnec ◽  
Hinnerk Eilers ◽  
Anika C. Jahns ◽  
Hélène Omer ◽  
Oleg A. Alexeyev
Keyword(s):  
Extracellular Matrix ◽  
Acne Vulgaris ◽  
Opportunistic Pathogen ◽  
Resistant Bacteria ◽  
Skin Microbiome ◽  
Cutibacterium Acnes ◽  
Propionibacterium Granulosum ◽  
Extracellular Nuclease

Acne vulgaris is the most common dermatological disorder worldwide affecting more than 80% of adolescents and young adults with a global prevalence of 231 million cases in 2019. The involvement of the skin microbiome disbalance in the pathophysiology of acne is recognized, especially regarding the relative abundance and diversity of Propionibacterium acnes a well-known dominant human skin commensal. Biofilms, where bacteria are embedded into a protective polymeric extracellular matrix, are the most prevalent life style for microorganisms. P. acnes and its biofilm-forming ability is believed to be a contributing factor in the development of acne vulgaris, the persistence of the opportunistic pathogen and antibiotic therapy failures. Degradation of the extracellular matrix is one of the strategies used by bacteria to disperse the biofilm of competitors. In this study, we report the identification of an endogenous extracellular nuclease, BmdE, secreted by Propionibacterium granulosum able to degrade P. acnes biofilm both in vivo and in vitro. This, to our knowledge, may represent a novel competitive mechanism between two closely related species in the skin. Antibiotics targeting P. acnes have been the mainstay in acne treatment. Extensive and long-term use of antibiotics has led to the selection and spread of resistant bacteria. The extracellular DNase BmdE may represent a new bio-therapeutical strategy to combat P. acnes biofilm in acne vulgaris.

scholarly journals Self-Nanoemulsion Loaded with a Combination of Isotretinoin, an Anti-Acne Drug, and Quercetin: Preparation, Optimization, and In Vivo Assessment

Pharmaceutics ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 46
Author(s):  
Khaled M. Hosny ◽  
Khalid S. Al Nahyah ◽  
Nabil A. Alhakamy
Keyword(s):  
Ex Vivo ◽  
Acne Vulgaris ◽  
Topical Administration ◽  
Hepatoprotective Activity ◽  
In Vivo Studies ◽  
Enhanced Solubility ◽  
Staphyloccocus Aureus ◽  
Common Skin

Acne vulgaris is a common skin disease that affects everybody at least once in their lives. The treatment is challenging because the stratum corneum contains rigid corneocytes surrounded by intercellular lamellae that are difficult to bypass. In the present study, we intended to formulate an effective nanoemulsion that could deliver isotretinoin (ITT) with enhanced solubility, permeability, and bioavailability across the skin. ITT can have a serious hepatotoxic effect if given too frequently or erratically. Therefore, to overcome the aforesaid limitation, quercetin (QRS), a hepatoprotective agent, was incorporated into the formulation. Initially, the ITT solubility was determined in various surfactants and cosurfactants to select the essential ingredients to be used in the formulation and to optimize a nanoemulsion that could enhance the solubility and permeability of ITT and its antimicrobial activity against Staphyloccocus aureus, which is the main microorganism responsible for acne vulgaris. The mixture design was applied to study the interactions and optimize the independent variables that could match the prerequisites of selected dependent responses. A formulation containing 0.25 g of rosehip oil, 0.45 g of surfactant (Lauroglycol-90), and 0.3 g of cosurfactant (propylene glycol) was chosen as an optimized desirable formulation. The optimized batch was loaded with QRS and evaluated for in vitro and ex vivo permeation. The in vivo hepatotoxicity was assessed through topical administration. Permeability studies confirmed the enhanced permeation percentage of ITT (52.11 ± 2.85%) and QRS (25.44 ± 3.18%) of the optimized formulation, with an enhanced steady-state flux (Jss). The in vivo studies conducted on experimental animals demonstrated superior hepatoprotective activity of the prepared optimized formulation compared with other formulations of drugs and commercially marketed products. We anticipate that this optimized ITT formulation, followed up with good clinical evaluations, can be a breakthrough in the safe treatment of acne vulgaris.

scholarly journals Topical Administration of Drugs Incorporated in Carriers Containing Phospholipid Soft Vesicles for the Treatment of Skin Medical Conditions

Pharmaceutics ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2129
Author(s):  
Elka Touitou ◽  
Hiba Natsheh
Keyword(s):  
Drug Delivery ◽  
Acne Vulgaris ◽  
Skin Barrier ◽  
Skin Inflammation ◽  
Topical Administration ◽  
Skin Aging ◽  
Oral Drug ◽  
Medical Conditions

This review focuses on the improved topical treatment of various medical skin conditions by the use of drugs delivered from carriers containing phospholipid soft vesicles. Topical drug delivery has many advantages over other ways of administration, having increased patient compliance, avoiding the first-pass effect following oral drug administration or not requesting multiple doses administration. However, the skin barrier prevents the access of the applied drug, affecting its therapeutic activity. Carriers containing phospholipid soft vesicles are a new approach to enhance drug delivery into the skin and to improve the treatment outcome. These vesicles contain molecules that have the property to fluidize the phospholipid bilayers generating the soft vesicle and allowing it to penetrate into the deep skin layers. Ethosomes, glycerosomes and transethosomes are soft vesicles containing ethanol, glycerol or a mixture of ethanol and a surfactant, respectively. We review a large number of publications on the research carried out in vitro, in vivo in animal models and in humans in clinical studies, with compositions containing various active molecules for treatment of skin medical conditions including skin infections, skin inflammation, psoriasis, skin cancer, acne vulgaris, hair loss, psoriasis and skin aging.

scholarly journals Electricity-producing Staphylococcus epidermidis counteracts Cutibacterium acnes

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shinta Marito ◽  
Sunita Keshari ◽  
Supitchaya Traisaeng ◽  
Do Thi Tra My ◽  
Arun Balasubramaniam ◽  
...  
Keyword(s):  
Staphylococcus Epidermidis ◽  
Acne Vulgaris ◽  
Cyclophilin A ◽  
Electrical Current ◽  
Suppressive Effect ◽  
Intradermal Injection ◽  
Electricity Production ◽  
Cutibacterium Acnes

AbstractStaphylococcus epidermidis (S. epidermidis) ATCC 12228 was incubated with 2% polyethylene glycol (PEG)-8 Laurate to yield electricity which was measured by a voltage difference between electrodes. Production of electron was validated by a Ferrozine assay. The anti-Cutibacterium acnes (C. acnes) activity of electrogenic S. epidermidis was assessed in vitro and in vivo. The voltage change (~ 4.4 mV) reached a peak 60 min after pipetting S. epidermidis plus 2% PEG-8 Laurate onto anodes. The electricity produced by S. epidermidis caused significant growth attenuation and cell lysis of C. acnes. Intradermal injection of C. acnes and S. epidermidis plus PEG-8 Laurate into the mouse ear considerably suppressed the growth of C. acnes. This suppressive effect was noticeably reversed when cyclophilin A of S. epidermidis was inhibited, indicating the essential role of cyclophilin A in electricity production of S. epidermidis against C. acnes. In summary, we demonstrate for the first time that skin S. epidermidis, in the presence of PEG-8 Laurate, can mediate cyclophilin A to elicit an electrical current that has anti-C. acnes effects. Electricity generated by S. epidermidis may confer immediate innate immunity in acne lesions to rein in the overgrowth of C. acnes at the onset of acne vulgaris.

scholarly journals Suppressive Effect of Two Cucurbitane-Type Triterpenoids from Momordica charantia on Cutibacterium acnes-Induced Inflammatory Responses in Human THP-1 Monocytic Cell and Mouse Models

Molecules ◽  
2021 ◽  
Vol 26 (3) ◽  
pp. 579
Author(s):  
Lu-Te Chuang ◽  
Wen-Cheng Huang ◽  
Yu-Chen Hou ◽  
Jong-Ho Chyuan ◽  
Hsiang Chang ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Acne Vulgaris ◽  
Bacterial Species ◽  
Suppressive Effect ◽  
Momordica Charantia ◽  
Monocytic Cell ◽  
Caspase 1 ◽  
Cutibacterium Acnes

Cutibacterium acnes (formerly Propionibacterium acnes) is one of the major bacterial species responsible for acne vulgaris. Numerous bioactive compounds from Momordica charantia Linn. var. abbreviata Ser. have been isolated and examined for many years. In this study, we evaluated the suppressive effect of two cucurbitane-type triterpenoids, 5β,19-epoxycucurbita-6,23-dien-3β,19,25-triol (Kuguacin R; KR) and 3β,7β,25-trihydroxycucurbita-5,23-dien-19-al (TCD) on live C. acnes-stimulated in vitro and in vivo inflammatory responses. Using human THP-1 monocytes, KR or TCD suppressed C. acnes-induced production of interleukin (IL)-1β, IL-6 and IL-8 at least above 56% or 45%, as well as gene expression of these three pro-inflammatory cytokines. However, a significantly strong inhibitory effect on production and expression of tumor necrosis factor (TNF)-α was not observed. Both cucurbitanes inhibited C. acnes-induced activation of the myeloid differentiation primary response 88 (MyD88) (up to 62%) and mitogen-activated protein kinases (MAPK) (at least 36%). Furthermore, TCD suppressed the expression of pro-caspase-1 and cleaved caspase-1 (p10). In a separate study, KR or TCD decreased C. acnes-stimulated mouse ear edema by ear thickness (20% or 14%), and reduced IL-1β-expressing leukocytes and neutrophils in mouse ears. We demonstrated that KR and TCD are potential anti-inflammatory agents for modulating C. acnes-induced inflammation in vitro and in vivo.

scholarly journals Novel Rifampicin and Indocyanine Green Co-Loaded Perfluorocarbon Nanodroplets Provide Effective In Vivo Photo–Chemo–Probiotic Antimicrobility against Pathogen of Acne Vulgaris Cutibacterium acnes

Nanomaterials ◽  
2020 ◽  
Vol 10 (6) ◽  
pp. 1095
Author(s):  
Kuang-Hung Hsiao ◽  
Chun-Ming Huang ◽  
Yu-Hsiang Lee
Keyword(s):  
Indocyanine Green ◽  
Staphylococcus Epidermidis ◽  
Near Infrared ◽  
Acne Vulgaris ◽  
Inhibition Zone ◽  
Inflammatory Protein ◽  
Cutibacterium Acnes ◽  
Macrophage Inflammatory Protein

Acne vulgaris is one of the most prevalent dermatological diseases among adolescents and is often associated with overgrowth of Cutibacterium acnes (C. acnes) in the pilosebaceous units. In this study, we aimed to develop novel rifampicin (RIF) and indocyanine green (ICG) co-loaded perfluorocarbon nanodroplets named RIPNDs which can simultaneously provide photo-, chemo-, and probiotic-antimicrobility, and explore their efficacy in treatment of C. acnes in vitro and in vivo. The RIPNDs were first characterized as being spherical in shape, with a size of 238.6 ± 7.51 nm and surface charge of −22.3 ± 3.5 mV. Then, the optimal dosages of Staphylococcus epidermidis–produced fermentation product medium (FPM) and RIPND were determined as 25% (v/v) and [RIF]/[ICG] = 3.8/20 μM, respectively, based on the analyses of inhibition zone and cytotoxicity in vitro. Through the in vivo study using C. acnes–inoculated mice, our data showed that the group treated with FPM followed by RIPNDs + near infrared (NIR) irradiation obtained the least granulocytes/macrophage-inflammatory protein 2 expression level in the epidermis, and showed a significantly lower microbial colony population compared to the groups treated with equal amount of RIF, FPM, RIPNDs, and/or combination of the above ± NIR. These results indicated that the RIPND-mediated photo–chemo–probiotic therapeutics was indeed able to rapidly suppress inflammatory response of the skin and provide a robust antibacterial effect against C. acnes with limited use of antibiotics. Taken altogether, we anticipate that the RIPND is highly potential for use in the clinical treatment of acne vulgaris.

scholarly journals Electricity-Producing Staphylococcus Epidermidis Counteracts Cutibacterium Acnes

2021 ◽  
Author(s):  
Shinta Marito ◽  
Sunita Keshari ◽  
Supitchaya Traisaeng ◽  
Do Thi Tra My ◽  
Arun Balasubramaniam ◽  
...  
Keyword(s):  
Staphylococcus Epidermidis ◽  
Acne Vulgaris ◽  
Cyclophilin A ◽  
Electrical Current ◽  
Suppressive Effect ◽  
Intradermal Injection ◽  
Electricity Production ◽  
Cutibacterium Acnes

Abstract Staphylococcus epidermidis (S. epidermidis) ATCC 12228 was incubated with 2% polyethylene glycol (PEG)-8 Laurate to yield electricity which was measured by a voltage difference between electrodes. Production of electron was validated by a Ferrozine assay. The anti-Cutibacterium acnes (C. acnes) activity of electrogenic S. epidermidis was assessed in vitro and in vivo. The voltage change (~ 4.4 mV) reached a peak 60 minutes after pipetting S. epidermidis plus 2% PEG-8 Laurate onto anodes. The electricity produced by S. epidermidis caused significant growth attenuation and cell lysis of C. acnes. Intradermal injection of C. acnes and S. epidermidis plus PEG-8 Laurate into the mouse ear considerably suppressed the growth of C. acnes. This suppressive effect was noticeably reversed when cyclophilin A of S. epidermidis was inhibited, indicating the essential role of cyclophilin A in electricity production of S. epidermidis against C. acnes. In summary, we demonstrate for the first time that skin S. epidermidis, in the presence of PEG-8 Laurate, can mediate cyclophilin A to elicit an electrical current that has anti-C. acnes effects. Electricity generated by S. epidermidis may confer immediate innate immunity in acne lesions to rein in the overgrowth of C. acnes at the onset of acne vulgaris.

scholarly journals Pro-Inflammatory and Neurotrophic Factor Responses of Cells Derived from Degenerative Human Intervertebral Discs to the Opportunistic Pathogen Cutibacterium acnes

2021 ◽  
Vol 22 (5) ◽  
pp. 2347
Author(s):  
Manu N. Capoor ◽  
Anna Konieczna ◽  
Andrew McDowell ◽  
Filip Ruzicka ◽  
Martin Smrcka ◽  
...  
Keyword(s):  
Neurotrophic Factor ◽  
Acne Vulgaris ◽  
Opportunistic Pathogen ◽  
Intervertebral Discs ◽  
Disc Disease ◽  
Gene Target ◽  
Cutibacterium Acnes ◽  
Pre Treatment

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.

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