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1.
Adv Exp Med Biol ; 1447: 117-129, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38724789

RESUMEN

With recent advances in topical therapies for atopic dermatitis (AD), steroid-sparing options like calcineurin inhibitors, Janus kinase (JAK) inhibitors, and phosphodiesterase-4 (PDE-4) inhibitors are becoming mainstays in therapy, underscoring the importance of careful selection and usage of topical corticosteroids (TCSs) to minimize side effects. Alongside the necessity of emollient use, these steroid-sparing alternatives offer rapid itch relief and efficacy in improving disease severity. While TCSs still hold a prominent role in AD management, promising novel topical treatments like tapinarof and live biotherapeutics to modulate the skin microbiome are also discussed. Overall, the recent addition of novel topical therapies offers diverse options for AD management and underscores the importance of topical treatments in the management of AD.


Asunto(s)
Dermatitis Atópica , Humanos , Dermatitis Atópica/tratamiento farmacológico , Dermatitis Atópica/microbiología , Administración Tópica , Corticoesteroides/uso terapéutico , Corticoesteroides/administración & dosificación , Inhibidores de Fosfodiesterasa 4/uso terapéutico , Administración Cutánea , Piel/efectos de los fármacos , Piel/microbiología , Piel/patología , Inhibidores de la Calcineurina/uso terapéutico , Inhibidores de la Calcineurina/administración & dosificación , Fármacos Dermatológicos/uso terapéutico , Fármacos Dermatológicos/administración & dosificación , Fármacos Dermatológicos/efectos adversos
2.
Sci Rep ; 14(1): 10193, 2024 05 03.
Artículo en Inglés | MEDLINE | ID: mdl-38702361

RESUMEN

Amphibians are often recognized as bioindicators of healthy ecosystems. The persistence of amphibian populations in heavily contaminated environments provides an excellent opportunity to investigate rapid vertebrate adaptations to harmful contaminants. Using a combination of culture-based challenge assays and a skin permeability assay, we tested whether the skin-associated microbiota may confer adaptive tolerance to tropical amphibians in regions heavily contaminated with arsenic, thus supporting the adaptive microbiome principle and immune interactions of the amphibian mucus. At lower arsenic concentrations (1 and 5 mM As3+), we found a significantly higher number of bacterial isolates tolerant to arsenic from amphibians sampled at an arsenic contaminated region (TES) than from amphibians sampled at an arsenic free region (JN). Strikingly, none of the bacterial isolates from our arsenic free region tolerated high concentrations of arsenic. In our skin permeability experiment, where we tested whether a subset of arsenic-tolerant bacterial isolates could reduce skin permeability to arsenic, we found that isolates known to tolerate high concentrations of arsenic significantly reduced amphibian skin permeability to this metalloid. This pattern did not hold true for bacterial isolates with low arsenic tolerance. Our results describe a pattern of environmental selection of arsenic-tolerant skin bacteria capable of protecting amphibians from intoxication, which helps explain the persistence of amphibian populations in water bodies heavily contaminated with arsenic.


Asunto(s)
Anfibios , Arsénico , Microbiota , Piel , Animales , Arsénico/metabolismo , Arsénico/toxicidad , Microbiota/efectos de los fármacos , Piel/microbiología , Piel/efectos de los fármacos , Piel/metabolismo , Anfibios/microbiología , Bacterias/efectos de los fármacos , Bacterias/clasificación , Bacterias/metabolismo , Bacterias/genética , Permeabilidad/efectos de los fármacos
3.
Zhonghua Yu Fang Yi Xue Za Zhi ; 58(5): 711-718, 2024 May 06.
Artículo en Chino | MEDLINE | ID: mdl-38715514

RESUMEN

The human body, as a highly complex ecosystem, harbors diverse microbial communities, with major factors triggering allergic reactions encompassing the skin microbiome and fungi. The global diversity of fungi is estimated to range from approximately 600 000 to 1 million species, and theoretically, IgE-mediated sensitization may occur to any fungal species. As of now, the World Health Organization/IUIS official database records 113 fungal allergens originating from 30 different fungi species, covering 42 allergen families. Regarding the skin microbiome, 14 distinct Malassezia allergens have been identified, all derived from three different Malassezia fungi species--M. furfur, M. sympodialis, and M. globosa. The conditions of patients with these allergies are exceptionally complex. This article extensively discusses the latest research advancements and clinical applications related to skin microbiome and fungal allergies from the European Academy of Allergy and Clinical Immunology (EAACI) publication, "Molecular Allergology User's Guide 2.0". Additionally, it compiles information on the sources of fungal allergens, characteristics of allergen component protein families, clinical relevance, and management strategies, both domestically and internationally. The aim is to enhance the profound understanding of allergen components among relevant professionals. Through the application of advanced allergen component diagnostic techniques, the goal is to achieve precise diagnosis and treatment of fungal allergy patients and explore the mechanisms underlying fungal sensitization and pathogenesis, laying the foundation for studying the fungal allergen protein sensitization spectrum in the Chinese population.


Asunto(s)
Alérgenos , Hongos , Hipersensibilidad , Microbiota , Alérgenos/inmunología , Humanos , Hongos/inmunología , Hipersensibilidad/diagnóstico , Proteínas Fúngicas/inmunología , Piel/microbiología , Malassezia/inmunología
4.
JCI Insight ; 9(9)2024 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-38716729

RESUMEN

Atopic dermatitis (AD) is an inflammatory skin condition with a childhood prevalence of up to 25%. Microbial dysbiosis is characteristic of AD, with Staphylococcus aureus the most frequent pathogen associated with disease flares and increasingly implicated in disease pathogenesis. Therapeutics to mitigate the effects of S. aureus have had limited efficacy and S. aureus-associated temporal disease flares are synonymous with AD. An alternative approach is an anti-S. aureus vaccine, tailored to AD. Experimental vaccines have highlighted the importance of T cells in conferring protective anti-S. aureus responses; however, correlates of T cell immunity against S. aureus in AD have not been identified. We identify a systemic and cutaneous immunological signature associated with S. aureus skin infection (ADS.aureus) in a pediatric AD cohort, using a combined Bayesian multinomial analysis. ADS.aureus was most highly associated with elevated cutaneous chemokines IP10 and TARC, which preferentially direct Th1 and Th2 cells to skin. Systemic CD4+ and CD8+ T cells, except for Th2 cells, were suppressed in ADS.aureus, particularly circulating Th1, memory IL-10+ T cells, and skin-homing memory Th17 cells. Systemic γδ T cell expansion in ADS.aureus was also observed. This study suggests that augmentation of protective T cell subsets is a potential therapeutic strategy in the management of S. aureus in AD.


Asunto(s)
Dermatitis Atópica , Infecciones Cutáneas Estafilocócicas , Staphylococcus aureus , Dermatitis Atópica/inmunología , Dermatitis Atópica/microbiología , Humanos , Staphylococcus aureus/inmunología , Niño , Femenino , Infecciones Cutáneas Estafilocócicas/inmunología , Infecciones Cutáneas Estafilocócicas/microbiología , Masculino , Preescolar , Piel/microbiología , Piel/inmunología , Piel/patología , Quimiocina CXCL10/inmunología , Quimiocina CXCL10/metabolismo , Células TH1/inmunología , Células Th2/inmunología , Células Th17/inmunología , Teorema de Bayes , Linfocitos T CD8-positivos/inmunología , Interleucina-10/metabolismo , Interleucina-10/inmunología , Linfocitos Intraepiteliales/inmunología , Antígenos de Diferenciación de Linfocitos T , Glicoproteínas de Membrana
5.
Front Immunol ; 15: 1352469, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38711504

RESUMEN

Vibriosis, caused by Vibrio, seriously affects the health of fish, shellfish, and shrimps, causing large economic losses. Teleosts are represent the first bony vertebrates with both innate and adaptive immune responses against pathogens. Aquatic animals encounter hydraulic pressure and more pathogens, compared to terrestrial animals. The skin is the first line of defense in fish, constituting the skin-associated lymphoid tissue (SALT), which belongs to the main mucosa-associated lymphoid tissues (MALT). However, little is known about the function of immunity related proteins in fish. Therefore, this study used iTRAQ (isobaric tags for relative and absolute quantitation) to compare the skin proteome between the resistant and susceptible families of Cynoglossus semilaevis. The protein integrin beta-2, the alpha-enolase isoform X1, subunit B of V-type proton ATPase, eukaryotic translation initiation factor 6, and ubiquitin-like protein ISG15, were highly expressed in the resistant family. The 16S sequencing of the skin tissues of the resistant and susceptible families showed significant differences in the microbial communities of the two families. The protein-microbial interaction identified ten proteins associated with skin microbes, including immunoglobulin heavy chain gene (IGH), B-cell lymphoma/leukemia 10 (BCL10) and pre-B-cell leukemia transcription factor 1 isoform X2 (PBX2). This study highlights the interaction between skin proteins and the microbial compositions of C. semilaevis and provides new insights into understanding aquaculture breeding research.


Asunto(s)
Resistencia a la Enfermedad , Enfermedades de los Peces , Proteínas de Peces , Peces Planos , Microbiota , Piel , Vibriosis , Vibrio , Animales , Piel/inmunología , Piel/microbiología , Piel/metabolismo , Enfermedades de los Peces/inmunología , Enfermedades de los Peces/microbiología , Resistencia a la Enfermedad/inmunología , Vibriosis/inmunología , Vibriosis/veterinaria , Peces Planos/inmunología , Peces Planos/microbiología , Microbiota/inmunología , Vibrio/inmunología , Proteínas de Peces/genética , Proteínas de Peces/metabolismo , Proteínas de Peces/inmunología , Proteoma , Proteómica/métodos
6.
J Photochem Photobiol B ; 255: 112909, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38669741

RESUMEN

Many common skin diseases are associated with changes in the microbiota. This applies for the commensal yeast Malassezia, which is linked to a wide range of skin disorders ranging from mild dandruff to severe seborrheic and atopic dermatitis, all of which have a detrimental impact on the individuals' quality of life. While antifungal medications offer relief in many cases, the challenges of disease recurrence and the emergence of resistance to the limited range of available antifungal drugs poses a pressing need for innovative therapeutic options. Here we examined the activity of water-filtered infrared A (wIRA) irradiation against Malassezia. wIRA's antimicrobial and wound healing properties make it an attractive option for localized, non-invasive, and contact-free treatment of superficial skin infections. Irradiation of Malassezia furfur with wIRA (570-1400 nm) resulted in a reduction of the yeast's metabolic activity. When put in contact with immune cells, wIRA-irradiated M. furfur was recovered at lower counts than non-irradiated M. furfur. Likewise, wIRA irradiation of M. furfur put in contact with keratinocytes, the primary host interface of the fungus in the skin, reduced the fungal counts, while the keratinocytes were not affected by the irradiation. The combination of wIRA with the photosensitizer methyl aminolevulinate exerted an additional antifungal effect on M. furfur, irrespective of the presence or absence of keratinocytes, suggesting an enhancement of the treatment effect when used in combination. These findings suggest that wIRA holds promise as a potential therapy for skin disorders associated with Malassezia.


Asunto(s)
Antifúngicos , Rayos Infrarrojos , Malassezia , Agua , Malassezia/efectos de la radiación , Malassezia/efectos de los fármacos , Humanos , Agua/química , Antifúngicos/farmacología , Antifúngicos/química , Piel/efectos de la radiación , Piel/microbiología , Queratinocitos/efectos de la radiación , Queratinocitos/efectos de los fármacos
7.
Int J Mol Sci ; 25(8)2024 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-38673985

RESUMEN

Antimicrobial resistance is a silent pandemic harming human health, and Pseudomonas aeruginosa is the most common bacterium responsible for chronic pulmonary and eye infections. Antimicrobial peptides (AMPs) represent promising alternatives to conventional antibiotics. In this review, the in vitro/in vivo activities of the frog skin-derived AMP Esc(1-21) are shown. Esc(1-21) rapidly kills both the planktonic and sessile forms of P. aeruginosa and stimulates migration of epithelial cells, likely favoring repair of damaged tissue. However, to undertake preclinical studies, some drawbacks of AMPs (cytotoxicity, poor biostability, and limited delivery to the target site) must be overcome. For this purpose, the stereochemistry of two amino acids of Esc(1-21) was changed to obtain the diastereomer Esc(1-21)-1c, which is more stable, less cytotoxic, and more efficient in treating P. aeruginosa-induced lung and cornea infections in mouse models. Incorporation of these peptides (Esc peptides) into nanoparticles or immobilization to a medical device (contact lens) was revealed to be an effective strategy to ameliorate and/or to prolong the peptides' antimicrobial efficacy. Overall, these data make Esc peptides encouraging candidates for novel multifunctional drugs to treat lung pathology especially in patients with cystic fibrosis and eye dysfunctions, characterized by both tissue injury and bacterial infection.


Asunto(s)
Infecciones por Pseudomonas , Pseudomonas aeruginosa , Animales , Pseudomonas aeruginosa/efectos de los fármacos , Infecciones por Pseudomonas/tratamiento farmacológico , Infecciones por Pseudomonas/microbiología , Humanos , Anuros , Piel/microbiología , Piel/efectos de los fármacos , Péptidos Antimicrobianos/farmacología , Péptidos Antimicrobianos/química , Péptidos Catiónicos Antimicrobianos/farmacología , Péptidos Catiónicos Antimicrobianos/uso terapéutico , Péptidos Catiónicos Antimicrobianos/química , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Antibacterianos/química
8.
Front Immunol ; 15: 1255859, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38646524

RESUMEN

Cutaneous T-cell lymphomas (CTCL) are a group of lymphoproliferative disorders of skin-homing T cells causing chronic inflammation. These disorders cause impairment of the immune environment, which leads to severe infections and/or sepsis due to dysbiosis. In this study, we elucidated the host-microbial interaction in CTCL that occurs during the phototherapeutic treatment regime and determined whether modulation of the skin microbiota could beneficially affect the course of CTCL. EL4 T-cell lymphoma cells were intradermally grafted on the back of C57BL/6 mice. Animals were treated with conventional therapeutics such as psoralen + UVA (PUVA) or UVB in the presence or absence of topical antibiotic treatment (neomycin, bacitracin, and polymyxin B sulphate) as an adjuvant. Microbial colonisation of the skin was assessed to correlate with disease severity and tumour growth. Triple antibiotic treatment significantly delayed tumour occurrence (p = 0.026), which prolonged the survival of the mice (p = 0.033). Allocation to phototherapeutic agents PUVA, UVB, or none of these, along with antibiotic intervention, reduced the tumour growth significantly (p = 0.0327, p ≤ 0.0001, p ≤ 0.0001 respectively). The beta diversity indices calculated using the Bray-Curtis model showed that the microbial population significantly differed after antibiotic treatment (p = 0.001). Upon modulating the skin microbiome by antibiotic treatment, we saw an increase in commensal Clostridium species, e.g., Lachnospiraceae sp. (p = 0.0008), Ruminococcaceae sp. (p = 0.0001)., Blautia sp. (p = 0.007) and a significant reduction in facultative pathogens Corynebacterium sp. (p = 0.0009), Pelomonas sp. (p = 0.0306), Streptococcus sp. (p ≥ 0.0001), Pseudomonas sp. (p = 0.0358), and Cutibacterium sp. (p = 0.0237). Intriguingly, we observed a significant decrease in Staphylococcus aureus frequency (p = 0.0001) but an increase in the overall detection frequency of the Staphylococcus genus, indicating that antibiotic treatment helped regain the microbial balance and increased the number of non-pathogenic Staphylococcus populations. These study findings show that modulating microbiota by topical antibiotic treatment helps to restore microbial balance by diminishing the numbers of pathogenic microbes, which, in turn, reduces chronic inflammation, delays tumour growth, and increases survival rates in our CTCL model. These findings support the rationale to modulate the microbial milieu during the disease course of CTCL and indicate its therapeutic potential.


Asunto(s)
Linfoma Cutáneo de Células T , Ratones Endogámicos C57BL , Microbiota , Neoplasias Cutáneas , Piel , Animales , Microbiota/efectos de los fármacos , Ratones , Piel/microbiología , Piel/patología , Piel/inmunología , Piel/efectos de los fármacos , Neoplasias Cutáneas/microbiología , Neoplasias Cutáneas/inmunología , Neoplasias Cutáneas/patología , Linfoma Cutáneo de Células T/microbiología , Linfoma Cutáneo de Células T/patología , Linfoma Cutáneo de Células T/tratamiento farmacológico , Linfoma Cutáneo de Células T/terapia , Modelos Animales de Enfermedad , Antibacterianos/uso terapéutico , Antibacterianos/farmacología , Antibacterianos/administración & dosificación , Línea Celular Tumoral , Femenino , Humanos
11.
PLoS One ; 19(4): e0297907, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38568962

RESUMEN

The human skin virome, unlike commensal bacteria, is an under investigated component of the human skin microbiome. We developed a sensitive, quantitative assay to detect cutaneous human resident papillomaviruses (HPV) and polyomaviruses (HPyV) and we first used it to describe these viral populations at the skin surface of two patients with atopic dermatitis (AD) and psoriasis (PSO). We performed skin swabs on lesional and non-lesional skin in one AD and one PSO patient at M0, M1 and M3. After extraction, DNA was amplified using an original multiplex PCR technique before high throughput sequencing (HTS) of the amplicons (named AmpliSeq-HTS). Quantitative results were ultimately compared with monoplex quantitative PCRs (qPCRs) for previously detected viruses and were significantly correlated (R2 = 0.95, ρ = 0.75). Fifteen and 13 HPV types (mainly gamma and beta-HPVs) or HPyV species (mainly Merkel Cell Polyomavirus (MCPyV)) were detected on the skin of the AD and PSO patients, respectively. In both patients, the composition of the viral flora was variable across body sites but remained stable over time in non-lesional skin samples, mostly colonized with gamma-papillomaviruses. In lesional skin samples, beta-papillomaviruses and MCPyV were the major components of a viral flora more prone to vary over time especially with treatment and subsequent clinical improvement. We believe this method might be further used in extensive studies to further enhance the concept of an individual cutaneous viral fingerprint and the putative role of its alterations through various skin diseases and their treatments.


Asunto(s)
Dermatitis Atópica , Poliomavirus de Células de Merkel , Infecciones por Papillomavirus , Poliomavirus , Psoriasis , Enfermedades de la Piel , Humanos , Poliomavirus/genética , Virus del Papiloma Humano , ADN Viral/genética , ADN Viral/análisis , Piel/microbiología , Papillomaviridae/genética , Reacción en Cadena en Tiempo Real de la Polimerasa
12.
Cell Rep ; 43(4): 114022, 2024 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-38568806

RESUMEN

Staphylococcus aureus causes the majority of skin and soft tissue infections, but this pathogen only transiently colonizes healthy skin. However, this transient skin exposure enables S. aureus to transition to infection. The initial adhesion of S. aureus to skin corneocytes is mediated by surface protein G (SasG). Here, phylogenetic analyses reveal the presence of two major divergent SasG alleles in S. aureus: SasG-I and SasG-II. Structural analyses of SasG-II identify a nonaromatic arginine in the binding pocket of the lectin subdomain that mediates adhesion to corneocytes. Atomic force microscopy and corneocyte adhesion assays indicate that SasG-II can bind to a broader variety of ligands than SasG-I. Glycosidase treatment results in different binding profiles between SasG-I and SasG-II on skin cells. In addition, SasG-mediated adhesion is recapitulated using differentiated N/TERT keratinocytes. Our findings indicate that SasG-II has evolved to adhere to multiple ligands, conferring a distinct advantage to S. aureus during skin colonization.


Asunto(s)
Adhesión Bacteriana , Queratinocitos , Piel , Staphylococcus aureus , Staphylococcus aureus/metabolismo , Humanos , Piel/microbiología , Piel/metabolismo , Queratinocitos/microbiología , Queratinocitos/metabolismo , Lectinas/metabolismo , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/genética , Filogenia , Unión Proteica
13.
Front Cell Infect Microbiol ; 14: 1307374, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38660491

RESUMEN

Cutaneous diseases (such as atopic dermatitis, acne, psoriasis, alopecia and chronic wounds) rank as the fourth most prevalent human disease, affecting nearly one-third of the world's population. Skin diseases contribute to significant non-fatal disability globally, impacting individuals, partners, and society at large. Recent evidence suggests that specific microbes colonising our skin and its appendages are often overrepresented in disease. Therefore, manipulating interactions of the microbiome in a non-invasive and safe way presents an attractive approach for management of skin and hair follicle conditions. Due to its proven anti-microbial and anti-inflammatory effects, blue light (380 - 495nm) has received considerable attention as a possible 'magic bullet' for management of skin dysbiosis. As humans, we have evolved under the influence of sun exposure, which comprise a significant portion of blue light. A growing body of evidence indicates that our resident skin microbiome possesses the ability to detect and respond to blue light through expression of chromophores. This can modulate physiological responses, ranging from cytotoxicity to proliferation. In this review we first present evidence of the diverse blue light-sensitive chromophores expressed by members of the skin microbiome. Subsequently, we discuss how blue light may impact the dialog between the host and its skin microbiome in prevalent skin and hair follicle conditions. Finally, we examine the constraints of this non-invasive treatment strategy and outline prospective avenues for further research. Collectively, these findings present a comprehensive body of evidence regarding the potential utility of blue light as a restorative tool for managing prevalent skin conditions. Furthermore, they underscore the critical unmet need for a whole systems approach to comprehend the ramifications of blue light on both host and microbial behaviour.


Asunto(s)
Luz Azul , Microbiota , Piel , Animales , Humanos , Disbiosis/microbiología , Piel/microbiología , Piel/efectos de la radiación , Enfermedades de la Piel/microbiología
14.
Sci Rep ; 14(1): 8245, 2024 04 08.
Artículo en Inglés | MEDLINE | ID: mdl-38589670

RESUMEN

The human skin microbiome comprises diverse populations that differ temporally between body sites and individuals. The virome is a less studied component of the skin microbiome and the study of bacteriophages is required to increase knowledge of the modulation and stability of bacterial communities. Staphylococcus species are among the most abundant colonisers of skin and are associated with both health and disease yet the bacteriophages infecting the most abundant species on skin are less well studied. Here, we report the isolation and genome sequencing of 40 bacteriophages from human skin swabs that infect coagulase-negative Staphylococcus (CoNS) species, which extends our knowledge of phage diversity. Six genetic clusters of phages were identified with two clusters representing novel phages, one of which we characterise and name Alsa phage. We identified that Alsa phages have a greater ability to infect the species S. hominis that was otherwise infected less than other CoNS species by the isolated phages, indicating an undescribed barrier to phage infection that could be in part due to numerous restriction-modification systems. The extended diversity of Staphylococcus phages here enables further research to define their contribution to skin microbiome research and the mechanisms that limit phage infection.


Asunto(s)
Bacteriófagos , Humanos , Bacteriófagos/genética , Coagulasa/genética , Genoma Viral , Piel/microbiología , Fagos de Staphylococcus/genética , Staphylococcus/genética
15.
J Invest Dermatol ; 144(5): 1001-1009, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38573278

RESUMEN

Whereas clinically apparent atopic dermatitis (AD) can be confirmed by validated diagnostic criteria, the preclinical phenotype of infants who eventually develop AD is less well-characterized. Analogous to unaffected or nonlesional skin in established AD, clinically normal-appearing skin in infants who will develop clinical AD has distinct changes. Prospective studies have revealed insights into this preclinical AD phenotype. In this study, we review the structural, immunologic, and microbiome nature of the preclinical AD phenotype. Determination of markers that predict the development of AD will facilitate targeting of interventions to prevent the development or reduce the severity of AD in infants.


Asunto(s)
Dermatitis Atópica , Piel , Humanos , Lactante , Biomarcadores/análisis , Dermatitis Atópica/inmunología , Dermatitis Atópica/microbiología , Dermatitis Atópica/diagnóstico , Microbiota/inmunología , Fenotipo , Índice de Severidad de la Enfermedad , Piel/microbiología , Piel/inmunología , Piel/patología
16.
Int J Biol Macromol ; 266(Pt 2): 131383, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38580030

RESUMEN

The development of antibiotic-loaded microneedles has been hindered for years by limited excipient options, restricted drug-loading space, poor microneedle formability, and short-term drug retention. Therefore, this study proposes a dissolving microneedle fabricated from the host-defense peptide ε-poly-l-lysine (EPL) as an antibacterial adjuvant system for delivering antibiotics. EPL serves not only as a major matrix material for the microneedle tips, but also as a broad-spectrum antibacterial agent that facilitates the intracellular accumulation of the antibiotic doxycycline (DOX) by increasing bacterial cell membrane permeability. Furthermore, the formation of physically crosslinked networks of EPL affords microneedle tips with improved formability, good mechanical properties, and amorphous nanoparticles (approximately 7.2 nm) of encapsulated DOX. As a result, a high total loading content of both antimicrobials up to 2319.1 µg/patch is achieved for efficient transdermal drug delivery. In a Pseudomonas aeruginosa-induced deep cutaneous infection model, the EPL microneedles demonstrates potent and long-term effects by synergistically enhancing antibiotic activities and prolonging drug retention in infected lesions, resulting in remarkable therapeutic efficacy with 99.91 % (3.04 log) reduction in skin bacterial burden after a single administration. Overall, our study highlights the distinct advantages of EPL microneedles and their potential in clinical antibacterial practice when loaded with amorphous DOX nanoparticles.


Asunto(s)
Antibacterianos , Doxiciclina , Nanopartículas , Agujas , Polilisina , Polilisina/química , Doxiciclina/administración & dosificación , Doxiciclina/farmacología , Doxiciclina/química , Nanopartículas/química , Antibacterianos/farmacología , Antibacterianos/administración & dosificación , Antibacterianos/química , Animales , Pseudomonas aeruginosa/efectos de los fármacos , Ratones , Sistemas de Liberación de Medicamentos , Administración Cutánea , Piel/efectos de los fármacos , Piel/microbiología , Infecciones por Pseudomonas/tratamiento farmacológico
17.
J Microbiol ; 62(3): 181-199, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38625646

RESUMEN

The interplay between the skin microbiome and its host is a complex facet of dermatological health and has become a critical focus in the development of microbiome cosmetics. The skin microbiome, comprising various microorganisms, is essential from birth, develops over the lifespan, and performs vital roles in protecting our body against pathogens, training the immune system, and facilitating the breakdown of organic matter. Dysbiosis, an imbalance of these microorganisms, has been implicated in a number of skin conditions such as acne, atopic dermatitis, and skin cancer. Recent scientific findings have spurred cosmetic companies to develop products that preserve and enhance the skin's microbial diversity balance. These products may incorporate elements like prebiotics, probiotics, and postbiotics, which are beneficial for the skin microbiome. Beyond topical products, there's increasing interest in ingestible beauty supplements (i.e. oral probiotics), highlighting the connection between the gut and skin. This review examines the influence of the microbiome on skin health and the emerging trends of microbiome skincare products.


Asunto(s)
Cosméticos , Microbiota , Probióticos , Piel , Humanos , Piel/microbiología , Probióticos/administración & dosificación , Prebióticos , Disbiosis/microbiología
18.
mBio ; 15(5): e0045324, 2024 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-38546267

RESUMEN

Staphylococcus aureus is a Gram-positive pathogen responsible for the majority of skin and soft tissue infections (SSTIs). S. aureus colonizes the anterior nares of approximately 20%-30% of the population and transiently colonizes the skin, thereby increasing the risk of developing SSTIs and more serious infections. Current laboratory models that mimic the skin surface environment are expensive, require substantial infrastructure, and limit the scope of bacterial physiology studies under human skin conditions. To overcome these limitations, we developed a cost-effective, open-source, chemically defined media recipe termed skin-like medium (SLM) that incorporates key aspects of the human skin surface environment and supports growth of several staphylococcal species. We utilized SLM to investigate the transcriptional response of methicillin-resistant Staphylococcus aureus (MRSA) following growth in SLM compared to a commonly used laboratory media. Through RNA-seq analysis, we observed the upregulation of several virulence factors, including genes encoding functions involved in adhesion, proteolysis, and cytotoxicity. To further explore these findings, we conducted quantitative reverse transcription-PCR (qRT-PCR) experiments to determine the influence of media composition, pH, and temperature on the transcriptional response of key factors involved in adhesion and virulence. We also demonstrated that MRSA primed in SLM adhered better to human corneocytes and demonstrated adhesin-specific phenotypes that previously required genetic manipulation. This improved adherence to corneocytes was dependent on both acidic pH and growth in SLM. These results support the potential utility of SLM as an in vitro model for assessing staphylococcal physiology and metabolism on human skin. IMPORTANCE: Staphylococcus aureus is the major cause of skin diseases, and its increased prevalence in skin colonization and infections present a need to understand its physiology in this environment. The work presented here outlines S. aureus upregulation of colonization and virulence factors using a newly developed medium that strives to replicate the human skin surface environment and demonstrates roles for adhesins clumping factor A (ClfA), serine-rich repeat glycoprotein adhesin (SraP), and the fibronectin binding proteins (Fnbps) in human corneocyte adherence.


Asunto(s)
Medios de Cultivo , Regulación Bacteriana de la Expresión Génica , Staphylococcus aureus Resistente a Meticilina , Piel , Factores de Virulencia , Humanos , Piel/microbiología , Staphylococcus aureus Resistente a Meticilina/genética , Staphylococcus aureus Resistente a Meticilina/fisiología , Factores de Virulencia/genética , Factores de Virulencia/metabolismo , Medios de Cultivo/química , Staphylococcus aureus/genética , Staphylococcus aureus/fisiología , Staphylococcus aureus/crecimiento & desarrollo , Staphylococcus aureus/patogenicidad , Infecciones Estafilocócicas/microbiología , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Adhesión Bacteriana
19.
J Dermatol Sci ; 114(1): 34-43, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38508974

RESUMEN

BACKGROUND: Vitiligo is an acquired pigmentary disorder characterized by depigmented patches on the skin that majorly impact patients' quality of life. Although its etiology involves genetic and environmental factors, the role of microorganisms as environmental factors in vitiligo pathology remains under-researched. OBJECTIVES: Our study explored the presence of characteristic bacterial and fungal flora in vitiligo-affected skin and investigated their potential roles in vitiligo pathogenesis. METHODS: We sequenced bacterial 16S rRNA and the fungal ITS1 region from skin swabs collected at frequently affected sites, namely the forehead and back, of patients with vitiligo. We analyzed bacterial and fungal flora in lesional and non-lesional areas of patients with vitiligo compared with corresponding sites in age- and sex-matched healthy subjects. RESULTS: Our findings revealed elevated α-diversity in both bacterial and fungal flora within vitiligo lesions compared with healthy controls. Notably, bacterial flora exhibited a distinctive composition in patients with vitiligo, and the proportional representation of Enterococcus was inversely correlated with the degree of vitiligo progression. Gammaproteobacteria, Staphylococcus spp., and Corynebacterium spp. were more abundant in vitiligo patients, with notable Staphylococcus spp. prevalence during the stable phase on the forehead. Conversely, the proportion of Malassezia sympodialis was lower and that of Malassezia globosa was higher in the progressive phase on the back of vitiligo patients. CONCLUSION: Our study identified some characteristic bacterial and fungal groups associated with vitiligo activity and prognosis, highlighting the potential roles of microorganisms in pathogenesis and offering insights into personalized disease-management approaches.


Asunto(s)
Microbiota , Micobioma , ARN Ribosómico 16S , Piel , Vitíligo , Humanos , Vitíligo/microbiología , Femenino , Masculino , Adulto , Piel/microbiología , Piel/patología , Persona de Mediana Edad , Japón , ARN Ribosómico 16S/genética , Estudios de Casos y Controles , Adulto Joven , Frente/microbiología , Dorso/microbiología , Malassezia/aislamiento & purificación , Corynebacterium/aislamiento & purificación , Staphylococcus/aislamiento & purificación , Pueblos del Este de Asia
20.
mSphere ; 9(4): e0055523, 2024 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-38530017

RESUMEN

Human cutaneous squamous cell carcinomas (SCCs) and actinic keratoses (AK) display microbial dysbiosis with an enrichment of staphylococcal species, which have been implicated in AK and SCC progression. SCCs are common in both felines and canines and are often diagnosed at late stages leading to high disease morbidity and mortality rates. Although recent studies support the involvement of the skin microbiome in AK and SCC progression in humans, there is no knowledge of this in companion animals. Here, we provide microbiome data for SCC in cats and dogs using culture-independent molecular profiling and show a significant decrease in microbial alpha diversity on SCC lesions compared to normal skin (P ≤ 0.05). Similar to human skin cancer, SCC samples had an elevated abundance of staphylococci relative to normal skin-50% (6/12) had >50% staphylococci, as did 16% (4/25) of perilesional samples. Analysis of Staphylococcus at the species level revealed an enrichment of the pathogenic species Staphylococcus felis in cat SCC samples, a higher prevalence of Staphylococcus pseudintermedius in dogs, and a higher abundance of Staphylococcus aureus compared to normal skin in both companion animals. Additionally, a comparison of previously published human SCC and perilesional samples against the present pet samples revealed that Staphylococcus was the most prevalent genera across human and companion animals for both sample types. Similarities between the microbial profile of human and cat/dog SCC lesions should facilitate future skin cancer research. IMPORTANCE: The progression of precancerous actinic keratosis lesions (AK) to cutaneous squamous cell carcinoma (SCC) is poorly understood in humans and companion animals, despite causing a significant burden of disease. Recent studies have revealed that the microbiota may play a significant role in disease progression. Staphylococcus aureus has been found in high abundance on AK and SCC lesions, where it secretes DNA-damaging toxins, which could potentiate tumorigenesis. Currently, a suitable animal model to investigate this relationship is lacking. Thus, we examined the microbiome of cutaneous SCC in pets, revealing similarities to humans, with increased staphylococci and reduced commensals on SCC lesions and peri-lesional skin compared to normal skin. Two genera that were in abundance in SCC samples have also been found in human oral SCC lesions. These findings suggest the potential suitability of pets as a model for studying microbiome-related skin cancer progression.


Asunto(s)
Carcinoma de Células Escamosas , Enfermedades de los Gatos , Enfermedades de los Perros , Microbiota , Neoplasias Cutáneas , Piel , Staphylococcus , Gatos , Perros , Animales , Carcinoma de Células Escamosas/microbiología , Carcinoma de Células Escamosas/veterinaria , Neoplasias Cutáneas/microbiología , Neoplasias Cutáneas/veterinaria , Neoplasias Cutáneas/patología , Piel/microbiología , Piel/patología , Enfermedades de los Gatos/microbiología , Staphylococcus/aislamiento & purificación , Staphylococcus/genética , Staphylococcus/clasificación , Staphylococcus/patogenicidad , Enfermedades de los Perros/microbiología , Queratosis Actínica/microbiología , Queratosis Actínica/veterinaria , Queratosis Actínica/patología
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