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1.
Immunity ; 50(4): 1069-1083.e8, 2019 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-30926233

RESUMO

Skin conventional dendritic cells (cDCs) exist as two distinct subsets, cDC1s and cDC2s, which maintain the balance of immunity to pathogens and tolerance to self and microbiota. Here, we examined the roles of dermal cDC1s and cDC2s during bacterial infection, notably Propionibacterium acnes (P. acnes). cDC1s, but not cDC2s, regulated the magnitude of the immune response to P. acnes in the murine dermis by controlling neutrophil recruitment to the inflamed site and survival and function therein. Single-cell mRNA sequencing revealed that this regulation relied on secretion of the cytokine vascular endothelial growth factor α (VEGF-α) by a minor subset of activated EpCAM+CD59+Ly-6D+ cDC1s. Neutrophil recruitment by dermal cDC1s was also observed during S. aureus, bacillus Calmette-Guérin (BCG), or E. coli infection, as well as in a model of bacterial insult in human skin. Thus, skin cDC1s are essential regulators of the innate response in cutaneous immunity and have roles beyond classical antigen presentation.


Assuntos
Acne Vulgar/imunologia , Células Dendríticas/classificação , Infecções por Bactérias Gram-Positivas/imunologia , Infiltração de Neutrófilos/imunologia , Fator A de Crescimento do Endotélio Vascular/imunologia , Acne Vulgar/microbiologia , Animais , Apresentação de Antígeno , Quimiotaxia de Leucócito/imunologia , Células Dendríticas/imunologia , Orelha Externa , Regulação da Expressão Gênica , Ontologia Genética , Infecções por Bactérias Gram-Positivas/microbiologia , Humanos , Injeções Intradérmicas , Camundongos , Camundongos Endogâmicos C57BL , Neutrófilos/metabolismo , Propionibacterium acnes , RNA Mensageiro/biossíntese , Análise de Célula Única , Fator A de Crescimento do Endotélio Vascular/biossíntese , Fator A de Crescimento do Endotélio Vascular/genética
2.
Nucleic Acids Res ; 51(6): 2915-2930, 2023 04 11.
Artigo em Inglês | MEDLINE | ID: mdl-36864821

RESUMO

Acne vulgaris is a chronic disfiguring skin disease affecting ∼1 billion people worldwide, often having persistent negative effects on physical and mental health. The Gram-positive anaerobe, Cutibacterium acnes is implicated in acne pathogenesis and is, therefore, a main target for antibiotic-based acne therapy. We determined a 2.8-Šresolution structure of the 70S ribosome of Cutibacterium acnes by cryogenic electron microscopy and discovered that sarecycline, a narrow-spectrum antibiotic against Cutibacterium acnes, may inhibit two active sites of this bacterium's ribosome in contrast to the one site detected previously on the model ribosome of Thermus thermophilus. Apart from the canonical binding site at the mRNA decoding center, the second binding site for sarecycline exists at the nascent peptide exit tunnel, reminiscent of the macrolides class of antibiotics. The structure also revealed Cutibacterium acnes-specific features of the ribosomal RNA and proteins. Unlike the ribosome of the Gram-negative bacterium Escherichia coli, Cutibacterium acnes ribosome has two additional proteins, bS22 and bL37, which are also present in the ribosomes of Mycobacterium smegmatis and Mycobacterium tuberculosis. We show that bS22 and bL37 have antimicrobial properties and may be involved in maintaining the healthy homeostasis of the human skin microbiome.


Assuntos
Acne Vulgar , Antibacterianos , Propionibacterium acnes , Ribossomos , Tetraciclinas , Humanos , Acne Vulgar/tratamento farmacológico , Acne Vulgar/microbiologia , Antibacterianos/química , Propionibacterium acnes/efeitos dos fármacos , Biossíntese de Proteínas , Ribossomos/efeitos dos fármacos , Tetraciclinas/farmacologia
3.
PLoS Pathog ; 18(3): e1010420, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35344565

RESUMO

Cutibacterium acnes (C. acnes) is a gram-positive bacterium and a member of the human skin microbiome. Despite being the most abundant skin commensal, certain members have been associated with common inflammatory disorders such as acne vulgaris. The availability of the complete genome sequences from various C. acnes clades have enabled the identification of putative methyltransferases, some of them potentially belonging to restriction-modification (R-M) systems which protect the host of invading DNA. However, little is known on whether these systems are functional in the different C. acnes strains. To investigate the activity of these putative R-M and their relevance in host protective mechanisms, we analyzed the methylome of six representative C. acnes strains by Oxford Nanopore Technologies (ONT) sequencing. We detected the presence of a 6-methyladenine modification at a defined DNA consensus sequence in strain KPA171202 and recombinant expression of this R-M system confirmed its methylation activity. Additionally, a R-M knockout mutant verified the loss of methylation properties of the strain. We studied the potential of one C. acnes bacteriophage (PAD20) in killing various C. acnes strains and linked an increase in its specificity to phage DNA methylation acquired upon infection of a methylation competent strain. We demonstrate a therapeutic application of this mechanism where phages propagated in R-M deficient strains selectively kill R-M deficient acne-prone clades while probiotic ones remain resistant to phage infection.


Assuntos
Acne Vulgar , Bacteriófagos , Acne Vulgar/genética , Acne Vulgar/microbiologia , Bacteriófagos/genética , Epigênese Genética , Humanos , Propionibacterium acnes/genética , Pele/microbiologia
4.
Microb Pathog ; 189: 106598, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38423403

RESUMO

Propionibacterium acnes (P. acnes) is an anaerobic and gram-positive bacterium involved in the pathogenesis and inflammation of acne vulgaris. This study particularly focuses on the antimicrobial effect of Lacticaseibacillus paracasei LPH01 against P. acnes, a bacterium that causes acne vulgaris. Fifty-seven Lactobacillus strains were tested for their ability to inhibit P. acnes growth employing the Oxford Cup and double dilution methods. The cell-free supernatant (CFS) of L. paracasei LPH01 demonstrated a strong inhibitory effect, with an inhibition zone diameter of 24.65 ± 0.27 mm and a minimum inhibitory concentration of 12.5 mg/mL. Among the CFS, the fraction over 10 kDa (CFS-10) revealed the best antibacterial effect. Confocal laser scanning microscopes and flow cytometry showed that CFS-10 could reduce cell metabolic activity and cell viability and destroy the integrity and permeability of the cell membrane. A scanning electron microscope revealed that bacterial cells exhibited obvious morphological and ultrastructural changes, which further confirmed the damage of CFS-10 to the cell membrane and cell wall. Findings demonstrated that CFS-10 inhibited the conversion of triglycerides, decreased the production of free fatty acids, and down-regulated the extracellular expression of the lipase gene. This study provides a theoretical basis for the metabolite of L. paracasei LPH01 as a potential antibiotic alternative in cosmeceutical skincare products.


Assuntos
Acne Vulgar , Lacticaseibacillus paracasei , Humanos , Propionibacterium acnes , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Acne Vulgar/tratamento farmacológico , Acne Vulgar/microbiologia , Inflamação/tratamento farmacológico , Testes de Sensibilidade Microbiana
5.
Microb Pathog ; 194: 106834, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39094711

RESUMO

Acne is one of the most common skin conditions worldwide, with multifactorial origins it affects areas of the skin with hair follicles and sebaceous glands that become clogged. Bacterial incidence aggravates treatment due to resistance to antimicrobial agents and production of virulence factors such as biofilm formation. Based on these information, this study aims to conduct in vitro evaluations of the antibacterial activity of essential oils (EOs), alone and in combination, against Propionibacterium acnes, Staphylococcus aureus, and Staphylococcus epidermidis in planktonic and biofilm forms. This study also assessed the anti-inflammatory potential (TNF-α) and the effects of EOs on the viability of human keratinocytes (HaCaT), murine fibroblasts (3T3-L1), and bone marrow-derived macrophages (BMDMs). Of all EOs tested, 13 had active action against P. acnes, 9 against S. aureus, and 9 against S. epidermidis at concentrations of 0.125-2.0 mg/mL. Among the most active plant species, a blend of essential oil (BEOs) was selected, with Cymbopogon martini (Roxb.) Will. Watson, Eugenia uniflora L., and Varronia curassavica Jacq., the latter due to its anti-inflammatory action. This BEOs showed higher inhibition rates when compared to chloramphenicol against S. aureus and S. epidermidis, and higher eradication rates when compared to chloramphenicol for the three target species. The BEOs did not affect the cell viability of cell lines evaluated, and the levels of TNF-α decreased. According to these results, the BEOs evaluated showed potential for the development of an alternative natural formulation for the treatment of acne.


Assuntos
Acne Vulgar , Antibacterianos , Anti-Inflamatórios , Biofilmes , Queratinócitos , Macrófagos , Testes de Sensibilidade Microbiana , Óleos Voláteis , Propionibacterium acnes , Staphylococcus aureus , Staphylococcus epidermidis , Fator de Necrose Tumoral alfa , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Óleos Voláteis/farmacologia , Humanos , Acne Vulgar/microbiologia , Acne Vulgar/tratamento farmacológico , Camundongos , Anti-Inflamatórios/farmacologia , Antibacterianos/farmacologia , Propionibacterium acnes/efeitos dos fármacos , Staphylococcus epidermidis/efeitos dos fármacos , Animais , Staphylococcus aureus/efeitos dos fármacos , Queratinócitos/efeitos dos fármacos , Queratinócitos/microbiologia , Macrófagos/efeitos dos fármacos , Macrófagos/microbiologia , Fator de Necrose Tumoral alfa/metabolismo , Fibroblastos/efeitos dos fármacos , Fibroblastos/microbiologia , Sobrevivência Celular/efeitos dos fármacos , Células HaCaT , Linhagem Celular , Óleos de Plantas/farmacologia
6.
Exp Dermatol ; 33(8): e15150, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39113601

RESUMO

Acne is a chronic inflammatory skin condition that involves Cutibacterium acnes (C. acnes), which is classified into six main phylotypes (IA1, IA2, IB, IC, II and III). Acne development is associated with loss of C. acnes phylotype diversity, characterised by overgrowth of phylotype IA1 relative to other phylotypes. It was also shown that purified extracellular vesicles (EVs) secreted by C. acnes can induce an acne-like inflammatory response in skin models. We aimed to determine if the inflammatory profile of EVs secreted by C. acnes phylotype IA1 from an inflammatory acne lesion was different from C. acnes phylotype IA1 from normal skin, thus playing a direct role in the severity of inflammation. EVs were produced in vitro after culture of two clinical strains of C. acnes phylotype IA1, T5 from normal human skin and A47 from an inflammatory acne lesion, and then incubated with either human immortalised keratinocytes, HaCaT cells, or skin explants obtained from abdominoplasty. Subsequently, quantitative PCR (qPCR) was performed for human ß-defensin 2 (hBD2), cathelicidin (LL-37), interleukin (IL)-1ß, IL-6, IL-8, IL-17α and IL-36γ, and ELISA for IL-6, IL-8 and IL-17α. We found that EVs produced in vitro by C. acnes derived from inflammatory acne lesions significantly increased the pro-inflammatory cytokines and anti-microbial peptides at both transcriptional and protein levels compared with EVs derived from normal human skin. We show for the first time that C. acnes EVs from inflammatory acne play a crucial role in acne-associated inflammation in vitro and that C. acnes phylotype IA1 collected from inflammatory acne lesion and normal skin produce different EVs and inflammatory profiles in vitro.


Assuntos
Acne Vulgar , Vesículas Extracelulares , Queratinócitos , Propionibacterium acnes , Humanos , Vesículas Extracelulares/metabolismo , Acne Vulgar/microbiologia , Queratinócitos/microbiologia , Pele/microbiologia , Inflamação/microbiologia , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Células HaCaT , Interleucina-1alfa/metabolismo , Interleucina-1beta/metabolismo , Citocinas/metabolismo , Interleucina-17/metabolismo , Propionibacteriaceae
7.
J Appl Microbiol ; 135(8)2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-39090975

RESUMO

As our understanding of dermatological conditions advances, it becomes increasingly evident that traditional pharmaceutical interventions are not universally effective. The intricate balance of the skin microbiota plays a pivotal role in the development of various skin conditions, prompting a growing interest in probiotics, or live biotherapeutic products (LBPs), as potential remedies. Specifically, the topical application of LBPs to modulate bacterial populations on the skin has emerged as a promising approach to alleviate symptoms associated with common skin conditions. This review considers LBPs and their application in addressing a wide spectrum of dermatological conditions with particular emphasis on three key areas: acne, atopic dermatitis, and wound healing. Within this context, the critical role of strain selection is presented as a pivotal factor in effectively managing these dermatological concerns. Additionally, the review considers formulation challenges associated with probiotic viability and proposes a personalised approach to facilitate compatibility with the skin's unique microenvironment. This analysis offers valuable insights into the potential of LBPs in dermatological applications, underlining their promise in reshaping the landscape of dermatological treatments while acknowledging the hurdles that must be overcome to unlock their full potential.


Assuntos
Probióticos , Pele , Probióticos/uso terapêutico , Humanos , Pele/microbiologia , Acne Vulgar/microbiologia , Acne Vulgar/terapia , Acne Vulgar/tratamento farmacológico , Cicatrização , Dermatite Atópica/microbiologia , Dermatite Atópica/tratamento farmacológico , Dermatite Atópica/terapia , Microbiota , Dermatopatias/microbiologia , Dermatopatias/tratamento farmacológico , Dermatopatias/terapia , Produtos Biológicos/uso terapêutico
8.
Acta Derm Venereol ; 104: adv33206, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38751177

RESUMO

The relevance of the gut microbiota in some skin inflammatory diseases, including acne vulgaris, has been emphasized. Probiotics could play a role in the modulation of the microbiota, improving the clinical course of this disease. A 12-week randomized, double-blind, placebo-controlled, clinical trial with patients aged 12 to 30 years with acne vulgaris was conducted. The study product was a capsule composed of the probiotic Lacticaseibacillus rhamnosus (CECT 30031) and the cyanobacterium Arthrospira platensis (BEA_IDA_0074B). Patients with improvement in the Acne Global Severity Scale were 10/34 (29.41%) in the placebo group compared with 20/40 (50%) in the probiotic group (p = 0.03). A significant reduction (p = 0.03) in the number of non-inflammatory acne lesions was observed in the probiotic group (-18.60 [-24.38 to -12.82]) vs the placebo group (-10.54 [-17.43 to -3.66]). Regarding the number of total  lesions, a reduction almost reaching statistical significance (p = 0.06) was observed in the probiotic group (-27.94 [-36.35 to -19.53]) compared with the placebo group (-18.31 [-28.21 to -8.41]). In addition, patients with improvement attending the Global Acne Grading System were 7/34 (20.58%) in the placebo group vs 17/40 (42.50%) in the probiotic group (p = 0.02). The number of adverse events was similar in both groups. The probiotic used in this study was effective and well tolerated, and it should be considered for acne vulgaris patients.


Assuntos
Acne Vulgar , Lacticaseibacillus rhamnosus , Probióticos , Humanos , Probióticos/administração & dosagem , Probióticos/efeitos adversos , Probióticos/uso terapêutico , Acne Vulgar/microbiologia , Acne Vulgar/terapia , Acne Vulgar/tratamento farmacológico , Acne Vulgar/diagnóstico , Método Duplo-Cego , Adolescente , Masculino , Adulto Jovem , Feminino , Adulto , Resultado do Tratamento , Criança , Administração Oral , Índice de Gravidade de Doença , Microbioma Gastrointestinal/efeitos dos fármacos , Fatores de Tempo
9.
Skin Res Technol ; 30(7): e13806, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39044362

RESUMO

BACKGROUND: The disruption of the microbial community or dysbiosis alters the functional composition, metabolic activity, and local distribution of the microbiota leading the development of acne. The aim of this study is to evaluate the effect of a lotion containing a biotechnological phytocomplex, niacinamide, and succinic acid in the bacterial diversity of subjects with truncal mild-moderate acne and its clinical benefits due to microbiota changes. MATERIALS AND METHODS: Open, clinical study in 43 subjects with truncal mild-moderate acne treated with a lotion for 8 weeks. Bacterial diversity was analyzed by 16S rRNA gene sequencing of skin samples. Clinical effects were evaluated through IGA acne severity scale, biometric measurements, and safety. RESULTS: After 56 days of product's use, an increase in richness alpha diversity was found (p = 0.005), with a decrease in Cutibacterium acnes relative abundance (66.43% vs. 58.11%, p = 0.009). The clinical results showed a decrease in IGA score (27.59% decrease; p = 0.001), the inflammatory lesions (52.12% decrease, p = 0.006) and erythema (18.33% decrease, p = 0.007), and desquamation index (63.83% decrease, p = 0.02). The responder analysis of the IGA score showed that 60.47% of patients improved by at least one point at day 56. The product was well tolerated along the study. CONCLUSION: The use of the lotion on acneic skin was effective on rebalancing the microbiota, inhibiting biofilm formation and other virulence factors, reducing erythema and desquamation, and improving acne's severity.


Assuntos
Acne Vulgar , Microbiota , Pele , Humanos , Acne Vulgar/microbiologia , Acne Vulgar/tratamento farmacológico , Masculino , Microbiota/efeitos dos fármacos , Feminino , Adulto Jovem , Pele/microbiologia , Pele/patologia , Adulto , Adolescente , Creme para a Pele , Índice de Gravidade de Doença
10.
J Eur Acad Dermatol Venereol ; 38 Suppl 7: 3-11, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39051132

RESUMO

BACKGROUND: The skin microbiota is known to be imbalanced in acne vulgaris, but the changes occurring during the early stages of acne onset remain poorly described. OBJECTIVES: To characterize the skin microbiome of subclinical stages of acne in adults and adolescents. METHODS: The composition and diversity of the microbiota from non-lesional skin on the forehead of subjects with mild-to-moderate acne were compared to the ones from non-acne subjects. Analyses of skin swab samples were performed using high-throughput sequencing of the V1-V3 regions of the bacterial 16S ribosomal RNA gene, the tuf gene fragment of Staphylococcus species and the internal transcribed spacer (ITS1) region of the fungal rRNA gene to determine the relative abundance, alpha-diversity and beta-diversity of bacteria and fungi. RESULTS: Compared with non-acne subjects, acne subjects had a higher abundance of Cutibacterium (72.4% vs. 57.8%) and lower abundances of Corynebacterium (2.8% vs. 4.8%) and Streptococcus (1.4% vs. 3.2%). Bacterial alpha- and beta-diversity indices also differed significantly between the two groups, reflecting differences in richness, evenness, abundance and phylogenetic distance between bacterial populations. Differences were also observed at the level of Staphylococcus species: S. capitis was predominant in skin samples from non-acne subjects (46.7%), whereas S. epidermidis was the most abundant Staphylococcus species in non-lesional forehead skin areas of acne subjects (44.2%). Conversely, no significant between-group differences were found for fungi, with Malasseziales being the predominant order in both subject groups. CONCLUSION: Dysbiosis was observed very early in subclinical acne stages of the forehead skin, with the overall abundance, richness and evenness of the bacterial population being lower in acne than in non-acne skin samples. Dysbiosis was also found at the level of Staphylococcus species. The development of acne lesions could therefore be prevented by using a skin care product that rebalances facial skin microbiota at very early stages.


Assuntos
Acne Vulgar , Testa , Microbiota , Pele , Humanos , Acne Vulgar/microbiologia , Testa/microbiologia , Masculino , Adulto , Feminino , Pele/microbiologia , Adolescente , Adulto Jovem
11.
J Eur Acad Dermatol Venereol ; 38 Suppl 7: 12-20, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39051131

RESUMO

BACKGROUND: Acne vulgaris is a common chronic inflammatory disorder of the pilosebaceous unit, characterized by papules, pustules and/or nodules manifesting primarily on the face and/or upper back that can leave scars, post-inflammatory hyperpigmentation (PIH) and erythema (PIE). OBJECTIVE: To evaluate the anti-inflammatory properties of a protein-free sap extruded from Rhealba® oat plantlets and a Garcinia mangostana extract on Cutibacterium acnes-induced inflammation in vitro and assess the tolerability and efficacy of a dermocosmetic product containing these actives in subjects with mild-to-moderate acne. METHODS: Monocyte-derived dendritic cells (Mo-DCs) from acne patients were stimulated with a planktonic culture of C. acnes and cytokine production was evaluated before and after addition of the test extracts by RT-PCR and ELISA. The clinical study was conducted in subjects with mild-to-moderate acne who applied the product to their face and upper back twice-daily for 2 months. RESULTS: Cutibacterium acnes-induced IL-6, IL-12p40, IL-10 and TNFα synthesis was reduced by the addition of the Garcinia mangostana extract and oat sap in vitro. The clinical study included 54 subjects. The 2-month, twice-daily application of the test product to the whole face and acne-affected areas on the upper back was well tolerated. It led to significant decreases in the number of retentional (-21% for 69% of subjects at D57) and inflammatory (-35% for 79% of subjects at D57) acne lesions, as well as a decrease in Global Acne Evaluation severity scores (2.5 at D1, 2.2 at D29 and 2.1 at D57). The dermatologist also rated the product as effective or very effective in most subjects with PIE (82%; n = 33/40) and PIH (70%; n = 8/11) at D57. CONCLUSION: The actives demonstrated anti-inflammatory effects in vitro, and the dermocosmetic product showed good clinical efficacy and tolerability in subjects with mild-to-moderate acne, supporting the use of this product in acne management.


Assuntos
Acne Vulgar , Avena , Garcinia mangostana , Extratos Vegetais , Humanos , Acne Vulgar/tratamento farmacológico , Acne Vulgar/microbiologia , Garcinia mangostana/química , Extratos Vegetais/farmacologia , Feminino , Masculino , Adulto , Adulto Jovem , Adolescente , Índice de Gravidade de Doença , Propionibacterium acnes/efeitos dos fármacos
12.
J Drugs Dermatol ; 23(2): SF37896s4-SF378969s10, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38306149

RESUMO

Antibiotics, topical and oral, are a cornerstone in the treatment of acnes vulgaris specifically by targeting the skin bacterium Cutibacterium acnes. Billions of individuals have received antibiotics as part of their treatment resulting in a worldwide pandemic of antibiotic resistance not only for C. acnes but also many other pathogens. With the increasing prevalence of acne and exponentially increasing utilization of antibiotics, prescribers must urgently embrace the notion of antibiotic stewardship to maintain the efficacy of acne treatments while attenuating the rise of resistance. This paper serves as an update on C. acnes resistance to antibiotics commonly employed in the treatment of acne and the necessity of implementing benzoyl peroxide in the treatment regimen as monotherapy or combination antibiotic therapies for overcoming and preventing resistance. J Drugs Dermatol. 2024;23:1(Suppl 2):s4-10.


Assuntos
Acne Vulgar , Gestão de Antimicrobianos , Humanos , Farmacorresistência Bacteriana , Acne Vulgar/diagnóstico , Acne Vulgar/tratamento farmacológico , Acne Vulgar/microbiologia , Antibacterianos , Peróxido de Benzoíla/uso terapêutico , Propionibacterium acnes
13.
Mar Drugs ; 22(8)2024 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-39195459

RESUMO

Acne is one of the most common dermatological conditions, peaking during adolescence and early adulthood, affecting about 85% of individuals aged 12-24. Although often associated with teenage years, acne can occur at any age, impacting over 25% of women and 12% of men in their forties. Treatment strategies vary depending on the severity, including the use of topical gels or creams containing benzoyl peroxide and retinoids, antibiotics, and systemic or topical isotretinoin. However, these treatments can cause irritation, allergies, and other toxic side effects. Currently, there is no natural-based alternative for antibacterial photodynamic therapy targeting acne using marine drugs or extracts. Through a bioguided screening approach, we identified the ethanol extract of Skeletonema marinoi as highly phototoxic against three bacterial species associated with acne-Cutibacterium acnes, Staphylococcus aureus, and Staphylococcus epidermidis. This extract exhibited phototoxicity in planktonic bacteria under white and red light, disrupted bacterial biofilms, reduced sebum production but also showed phototoxicity in keratinocytes, highlighting the importance of the specific targeting of treatment areas. Further investigations, including fractionation and high-resolution structural analysis, linked the observed phototoxicity to a high concentration of pheophorbide a in the extract. Given its notable in vitro efficacy, this extract holds promising potential for clinical evaluation to manage mild acne. This discovery paves the way for further exploration of Skeletonema pigment extracts, extending their potential applications beyond acne phototherapy to include dermocosmetics, veterinary medicine, and other phototherapy uses.


Assuntos
Acne Vulgar , Staphylococcus epidermidis , Acne Vulgar/tratamento farmacológico , Acne Vulgar/microbiologia , Humanos , Staphylococcus epidermidis/efeitos dos fármacos , Antibacterianos/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Biofilmes/efeitos dos fármacos , Etanol/química , Propionibacteriaceae/efeitos dos fármacos , Fotoquimioterapia/métodos , Phaeophyceae/química , Queratinócitos/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Feminino
14.
Australas J Dermatol ; 65(4): 319-327, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38419189

RESUMO

BACKGROUND: Numerous inflammatory skin diseases are associated with the gut microbiota. Studies of the association between gut microbiota and inflammatory skin diseases have yielded conflicting results owing to confounding factors, and the causal relationship between them remains undetermined. METHODS: Two-sample Mendelian randomization (MR) was used to examine the association between gut microbiota and four common inflammatory skin diseases: acne, psoriasis, urticaria and atopic dermatitis. The summary statistics of the gut microbiota from the largest available genome-wide association study meta-analysis (n = 13,266) conducted by the MiBioGen consortium along with the summary statistics of the four diseases were obtained from the FinnGen consortium. Causal relationships were assessed using the inverse variance weighted (IVW), weighted median, MR-Egger and maximum likelihood methods, and several sensitivity analyses were performed to ensure the accuracy of the results. Finally, reverse and multivariable MR analyses were performed to verify the robustness of the results. RESULTS: We found causal associations of Bacteroidaceae [odds ratio (OR), 2.25; 95% confidence interval (CI), 1.48-3.42; pivw = 0.0001], Allisonella (OR, 1.42; 95% CI, 1.18-1.70; pivw = 0.0002) and Bacteroides (OR, 2.25; 95% CI, 1.48-3.42; pivw = 0.0001) with acne, the Eubacterium fissicatena group with psoriasis (OR, 1.22; 95% CI, 1.10-1.35; pivw = 0.0002) and Intestinibacter with urticaria (OR, 1.28; 95% CI, 1.13-1.45; pivw = 0.0001). These results were corrected for a false discovery rate. Sensitivity analyses were performed to validate the robustness of the associations and reverse MR confirmed that the results were not influenced by the reverse effect. CONCLUSION: Our study revealed that some gut microbiota are risk factors for inflammatory skin diseases, providing new information on potential therapeutic targets. Additionally, a possible association with the gut-skin axis was confirmed. Further research is required to elucidate the mechanisms underlying these relationships.


Assuntos
Acne Vulgar , Dermatite Atópica , Microbioma Gastrointestinal , Análise da Randomização Mendeliana , Psoríase , Humanos , Microbioma Gastrointestinal/genética , Psoríase/microbiologia , Psoríase/genética , Acne Vulgar/microbiologia , Dermatite Atópica/microbiologia , Urticária/microbiologia , Estudo de Associação Genômica Ampla
15.
Int J Mol Sci ; 25(9)2024 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-38731983

RESUMO

Acne vulgaris is a prevalent skin disorder affecting many young individuals, marked by keratinization, inflammation, seborrhea, and colonization by Cutibacterium acnes (C. acnes). Ellagitannins, known for their antibacterial and anti-inflammatory properties, have not been widely studied for their anti-acne effects. Chestnut (Castanea sativa Mill., C. sativa), a rich ellagitannin source, including castalagin whose acne-related bioactivity was previously unexplored, was investigated in this study. The research assessed the effect of C. sativa leaf extract and castalagin on human keratinocytes (HaCaT) infected with C. acnes, finding that both inhibited IL-8 and IL-6 release at concentrations below 25 µg/mL. The action mechanism was linked to NF-κB inhibition, without AP-1 involvement. Furthermore, the extract displayed anti-biofilm properties and reduced CK-10 expression, indicating a potential role in mitigating inflammation, bacterial colonization, and keratosis. Castalagin's bioactivity mirrored the extract's effects, notably in IL-8 inhibition, NF-κB inhibition, and biofilm formation at low µM levels. Other polyphenols, such as flavonol glycosides identified via LC-MS, might also contribute to the extract's biological activities. This study is the first to explore ellagitannins' potential in treating acne, offering insights for developing chestnut-based anti-acne treatments pending future in vivo studies.


Assuntos
Acne Vulgar , Fagaceae , Taninos Hidrolisáveis , Extratos Vegetais , Folhas de Planta , Humanos , Taninos Hidrolisáveis/farmacologia , Fagaceae/química , Acne Vulgar/microbiologia , Acne Vulgar/tratamento farmacológico , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Folhas de Planta/química , Queratinócitos/efeitos dos fármacos , Queratinócitos/metabolismo , NF-kappa B/metabolismo , Células HaCaT , Propionibacterium acnes/efeitos dos fármacos , Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Interleucina-8/metabolismo
16.
Antimicrob Agents Chemother ; 67(4): e0167922, 2023 04 18.
Artigo em Inglês | MEDLINE | ID: mdl-36943064

RESUMO

Acne vulgaris is a complex skin disease involving infection by Cutibacterium acnes, inflammation, and hyperkeratinization. We evaluated the activity of the retinoid 6-[3-(adamantyl)-4-hydroxyphenyl]-2-naphthalene carboxylic acid (CD437) and 16 other retinoid analogs as potential anti-C. acnes compounds and found that CD437 displayed the highest antimicrobial activity with an MIC against C. acnes (ATCC 6919 and HM-513) of 1 µg/mL. CD437 demonstrated an MBC of 2 µg/mL compared to up to 64 µg/mL for the retinoid adapalene and up to 16 µg/mL for tetracycline, which are commonly used clinically to treat acne. Membrane permeability assays demonstrated that exposure of C. acnes ATCC 6919 to CD437 damaged the integrity of C. acnes ATCC 6919 bacterial membranes, and this finding was confirmed with scanning electron microscopy. Additionally, CD437 downregulated the expression of C. acnes ATCC 6919 virulence factors, including the genes encoding Christie-Atkins-Munch-Petersen factor 1 (CAMP1), CAMP2, glycerol-ester hydrolase B (GehB), sialidase B, and neuraminidase. In a mouse skin infection model of C. acnes ATCC 6919, topical treatment with CD437 ameliorated skin lesions and reduced the bacterial burden in situ (P < 0.001). In human NHEK primary cells, CD437 reduced the transcriptional levels of the coding genes for inflammatory cytokines (interleukin-1α, ~10-fold; interleukin-6, ~20-fold; interleukin-8, ~30-fold; and tumor necrosis factor-alpha, ~6-fold) and downregulated the transcriptional levels of KRT10 (~10-fold), FLG (~4-fold), and TGM1 (~2-fold), indicating that CD437 can diminish inflammation and hyperkeratinization. In summary, CD437 deserves further attention for its dual function as a potential acne therapeutic that potentially acts on both the pathogen and the host.


Assuntos
Acne Vulgar , Retinoides , Camundongos , Animais , Humanos , Retinoides/metabolismo , Retinoides/uso terapêutico , Acne Vulgar/tratamento farmacológico , Acne Vulgar/microbiologia , Citocinas/metabolismo , Antibacterianos/uso terapêutico , Inflamação , Propionibacterium acnes
17.
Microb Pathog ; 175: 105982, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36621695

RESUMO

BACKGROUND: The pathophysiology of acne is complex and multifactorial. In recent years, fungal infections have increased significantly. OBJECTIVES: The purpose of this study was to evaluate the role of fungi in the etiopathogenesis of acne vulgaris. METHODS: This was a prospective case-control study. A total of 200 individuals (100 with acne vulgaris and 100 without acne vulgaris) were enrolled in the study. Direct microscopic investigation and culturing of the samples were done according to Clinical and Laboratory Standards Institute criteria. Descriptive analyses, independent sample t-tests, and chi-squared tests were used for statistical analysis. The subjects in the control group were paired by age and gender with the patients. RESULTS: Direct microscopic examination revealed hyphae in the samples of all subjects with acne and in the samples of four of the healthy controls. The cultures of 18 of the patients with acne vulgaris were positive for the following: 6 with Aspergillus spp., 7 with Penicillium spp., 3 with Cladosporium spp., 1 with Candida spp., and 1 with Acremonium spp. In addition, Candida spp. was observed in the cultures of two of the healthy controls. CONCLUSION: We conclude that fungi may be involved in the etiopathogenesis of acne vulgaris.


Assuntos
Acne Vulgar , Humanos , Estudos de Casos e Controles , Acne Vulgar/microbiologia , Acne Vulgar/patologia , Epiderme/patologia , Fungos
18.
Microb Pathog ; 180: 106111, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37084823

RESUMO

Cutibacterium acnes (C. acnes) is a symbiotic bacterium that plays an important role in the formation of acn e inflammatory lesions. As a common component of the acne microbiome, C. acnes phages have the potential to make a significant contribution to treating antibiotic-resistant strains of C. acnes. However, little is known about their genetic composition and diversity. In this study, a new lytic phage, Y3Z, infecting C. acne, was isolated and characterized. Electron microscopy analysis revealed this phage is a siphovirus. Phage Y3Z is composed of 29,160 bp with a GC content of 56.32%. The genome contains 40 open reading frames, 17 of which had assigned functions, while no virulence-related genes, antibiotic resistance genes or tRNA were identified. The one-step growth curve showed the burst size was 30 PFU (plaque-forming unit)/cell. And it exhibited tolerance over a broad range of pH and temperature ranges. Phage Y3Z could infect and lyse all C. acnes isolates tested, though the host range of PA6 was restricted to C. acnes. Based on the phylogenetic and comparative genomic analyses, Y3Z may represent a new siphovirus infecting C. acnes. Characterization of Y3Z will enrich our knowledge about the diversity of C. acnes phages and provide a potential arsenal for thetreatment of acne infection.


Assuntos
Acne Vulgar , Bacteriófagos , Humanos , Genoma Viral , Filogenia , Propionibacterium acnes/genética , Acne Vulgar/genética , Acne Vulgar/microbiologia
19.
Exp Dermatol ; 32(12): 2102-2111, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37846925

RESUMO

Acne is a chronic disease that often persists for years. Skin microbial communities play an essential role in the development of acne. However, limited information is available about the dynamic patterns of skin microbiota in acne. This study aimed to characterize microbial community changes in skin pores and surfaces of acne patients with varying disease time. In this study, a total of 70 skin samples from 22 subjects were collected and sequenced using 16S rRNA amplicon sequencing. Although microbial compositions in skin pores were similar over time, significant differences in microbial structure were observed on the skin surface, with the dominance of Cutibacterium in the first 3 years and replacement by Staphylococcus in 4-6 years. Lactobacillus and Acinetobacter were more abundant in the normal group and continuingly decreased with disease time on the skin surface. Microbial networks further revealed substantial increases in microbial interactions in the 4-6 years group in both skin surfaces and pores. These results demonstrate that the skin microbiota alters with the disease duration and may provide a potential guide in redirecting skin microbiota towards healthy states.


Assuntos
Acne Vulgar , Microbiota , Humanos , RNA Ribossômico 16S/genética , Estudos Transversais , Acne Vulgar/microbiologia , Pele/microbiologia , Microbiota/genética , Estudos de Coortes
20.
Exp Dermatol ; 32(9): 1350-1360, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37183301

RESUMO

Acne vulgaris is a disorder of the pilosebaceous unit that is primarily caused by hyperseborrhoea, colonization with Propionibacterium acnes, hyperkeratosis and an inflammatory response. Existing pharmacodynamic assessment methods primarily focus on a single causative factor at a certain time point, making it difficult to assess multiple factors simultaneously in real time. Therefore, it is crucial to establish a dynamic and nondestructive method for the assessment of acne in vivo. This study utilized four-dimensional optical imaging techniques to assess the pathogenic factors and pathological progression of acne. LSCI was employed to measure blood flow; TPEF was used to observe inflammatory changes (NAD(P)H) in epidermal granular layer cells and structural changes in collagen fibres in the dermal layer. Additionally, the dermatoscope was used to investigate the micro-characterization of the lesions. We observed that the epidermis in the lesion area was thickened, hair follicles were keratinized, and there was obvious inflammation and blood flow aggregation by optical imaging technology. Based on these findings, the pathological progression of this acne model could be divided into the inflammation phase, accompanied by bacterial colonization, and the reparative phase. These results provide a new perspective for the assessment of acne and offer an experimental basis for the selection of precise drugs for clinical use.


Assuntos
Acne Vulgar , Animais , Camundongos , Acne Vulgar/microbiologia , Pele/patologia , Epiderme/patologia , Folículo Piloso/patologia , Propionibacterium acnes , Inflamação/diagnóstico por imagem
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