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Nature Communications Dec 2023Acne is a dermatologic disease with a strong pathologic association with human commensal Cutibacterium acnes. Conspicuously, certain C. acnes phylotypes are associated...
Acne is a dermatologic disease with a strong pathologic association with human commensal Cutibacterium acnes. Conspicuously, certain C. acnes phylotypes are associated with acne, whereas others are associated with healthy skin. Here we investigate if the evolution of a C. acnes enzyme contributes to health or acne. Two hyaluronidase variants exclusively expressed by C. acnes strains, HylA and HylB, demonstrate remarkable clinical correlation with acne or health. We show that HylA is strongly pro-inflammatory, and HylB is modestly anti-inflammatory in a murine (female) acne model. Structural and phylogenic studies suggest that the enzymes evolved from a common hyaluronidase that acquired distinct enzymatic activity. Health-associated HylB degrades hyaluronic acid (HA) exclusively to HA disaccharides leading to reduced inflammation, whereas HylA generates large-sized HA fragments that drive robust TLR2-dependent pathology. Replacing an amino acid, Serine to Glycine near the HylA catalytic site enhances the enzymatic activity of HylA and produces an HA degradation pattern intermediate to HylA and HylB. Selective targeting of HylA using peptide vaccine or inhibitors alleviates acne pathology. We suggest that the functional divergence of HylA and HylB is a major driving force behind C. acnes health- and acne- phenotype and propose targeting of HylA as an approach for acne therapy.
Topics: Humans; Female; Animals; Mice; Hyaluronoglucosaminidase; Skin; Acne Vulgaris; Propionibacterium acnes; Amino Acids
PubMed: 38052825
DOI: 10.1038/s41467-023-43833-8 -
International Journal of Dermatology Sep 2021Acne vulgaris is a worldwide condition that has a complex pathophysiology. The knowledge of this pathology is clear in its four classic principles based on the... (Review)
Review
Acne vulgaris is a worldwide condition that has a complex pathophysiology. The knowledge of this pathology is clear in its four classic principles based on the pilosebaceous unit; there exists hyperkeratinization of its duct, increase of sebum production, anaerobic bacterias, and inflammatory response. However, new findings have explained the relationship that occurs inside the acne lesion. The immune system has a key role since it is stimulated by the other participants involved, such as phylotypes of Propionibacterium acnes (P. acnes), antimicrobial peptides (AMPs), sebaceous glands (SGs), matrix metalloproteinases (MMPs), and other immune system pathways.
Topics: Acne Vulgaris; Humans; Immune System; Propionibacterium acnes; Sebaceous Glands; Sebum
PubMed: 33426647
DOI: 10.1111/ijd.15415 -
Anais Brasileiros de Dermatologia 2017Acne fulminans is a rare and severe variant of acne. In Brazilian medical journals, cases are infrequently reported, confirming its rarity. We followed five young male...
Acne fulminans is a rare and severe variant of acne. In Brazilian medical journals, cases are infrequently reported, confirming its rarity. We followed five young male patients with this severe variant of cutaneous lesions, accompanied by also severe systemic symptoms: fever, anorexia, weight loss, and arthralgia. All had a good response to corticosteroids (prednisone), but had significant scarring.
Topics: Acne Vulgaris; Adolescent; Arthralgia; Disease Progression; Fever; Glucocorticoids; Humans; Male; Necrosis; Prednisone; Propionibacterium acnes; Severity of Illness Index; Superantigens; Young Adult
PubMed: 29267432
DOI: 10.1590/abd1806-4841.20176546 -
Frontiers in Cellular and Infection... 2017This review discusses the biology and behavior of (), a dominant bacterium species of the skin biogeography thought to be associated with transmission, recurrence and... (Review)
Review
This review discusses the biology and behavior of (), a dominant bacterium species of the skin biogeography thought to be associated with transmission, recurrence and severity of disease. More specifically, we discuss the ability of to invade and persist in epithelial cells and circulating macrophages to subsequently induce bouts of sarcoidosis, low-grade inflammation and metastatic cell growth in the prostate gland. Finally, we discuss the possibility of infiltrating the brain parenchyma to indirectly contribute to pathogenic processes in neurodegenerative disorders such as those observed in Parkinson's disease (PD).
Topics: Animals; Epithelial Cells; Host-Pathogen Interactions; Humans; Macrophages; Male; Neurodegenerative Diseases; Propionibacterium acnes; Prostate; Sarcoidosis; Skin
PubMed: 28352613
DOI: 10.3389/fcimb.2017.00081 -
Advances in Experimental Medicine and... 2022Acne vulgaris results from a complex interaction between environment and genetic factors. While colonization of the pilosebaceous unit with Propionibacterium was...
Acne vulgaris results from a complex interaction between environment and genetic factors. While colonization of the pilosebaceous unit with Propionibacterium was previously considered to be the main cause of acne, the contribution of host-related factors that allow the growth of the bacteria and its immune response against bacterial components are now considered to be more important. Many of these host characteristics have a genetic base that is either involved in the regulation of the immune responses or the steroid hormones metabolisms. This chapter aims to explore the functions of these genes and their role in the pathogenesis of acne.
Topics: Acne Vulgaris; Humans; Immunogenetics; Propionibacterium acnes; Skin
PubMed: 35286695
DOI: 10.1007/978-3-030-92616-8_6 -
Naunyn-Schmiedeberg's Archives of... Jul 2023Viaminate, a retinoic acid derivative developed in China, has been clinically used for acne treatment to regulate and control keratinocyte cell differentiation and...
Viaminate, a retinoic acid derivative developed in China, has been clinically used for acne treatment to regulate and control keratinocyte cell differentiation and proliferation, inhibit keratinization, reduce sebum secretion, and regulate immune and anti-inflammatory functions; however, its potential molecular mechanism has not yet been elucidated. Therefore, we induced ear acne in rats using Propionibacterium acnes and sebum application. Symptoms of ear redness, epidermal thickening, inflammatory reaction, keratin overproduction, subcutaneous oil, and triglyceride (TG) accumulation improved significantly in acne model rats treated with viaminate for 30 days. Transcriptome analysis of rat skin tissues suggested that viaminate had significant regulatory effects on fatty acid metabolism and cellular keratinization pathways. Molecular target prediction suggested that toll-like receptor 2 (TLR2) may be a key target of viaminate's therapeutic mechanism. Western blotting results confirmed that viaminate inhibited the TLR2 and its downstream pathways, nuclear factor-kappa B (NF-κB) [NF-κB inhibitor alpha (IκBα)/NF-κB-p65] and mitogen-activated protein kinases (MAPKs) [MAPK p38/c-Jun N-terminal kinase (JNK)/extracellular regulated kinase 1/2 (ERK1/2)] in acne vulgaris rats. In vitro studies revealed that viaminate treatment attenuated P. acnes proliferation and P. acnes-induced inflammatory response in human keratinocytes and has an inhibitory effect on the activation of NF-κB and MAPKs, while overexpression of TLR2 attenuated these effects. In conclusion, viaminate ameliorates P. acnes-induced acne by inhibiting the proliferation and inflammatory response of keratinocytes, ascribed to the deactivation of the TLR2-mediated NF-κB and MAPK pathways.
Topics: Rats; Humans; Animals; NF-kappa B; Propionibacterium acnes; Toll-Like Receptor 2; Tretinoin; Acne Vulgaris; Mitogen-Activated Protein Kinases
PubMed: 36757484
DOI: 10.1007/s00210-022-02379-0 -
Cutis Jul 2019Drug development continues to focus on the challenge of treating acne effectively and safely. Inflammation is a backdrop to the commonly cited elements of the... (Review)
Review
Drug development continues to focus on the challenge of treating acne effectively and safely. Inflammation is a backdrop to the commonly cited elements of the pathophysiology of acne: Propionibacterium acnes proliferation, increased sebum production with an increase in circulating androgens, and faulty keratinization. As such, there is increased emphasis on targeting inflammation and its effects. Vehicle innovations are optimizing existing active drugs and creating opportunities to deliver new compounds to the skin. Recently approved sarecycline is the first new chemical entity approved for acne in several years. It might be followed in coming years by other new actives, including clascoterone and cannabidiol (CBD).
Topics: Acne Vulgaris; Dermatologic Agents; Drug Delivery Systems; Drug Development; Humans; Inflammation; Propionibacterium acnes; Sebum; Tetracyclines
PubMed: 31487336
DOI: No ID Found -
BMC Genomics Feb 2016Propionibacterium acnes and Staphylococcus epidermidis live in close proximity on human skin, and both bacterial species can be isolated from normal and acne...
BACKGROUND
Propionibacterium acnes and Staphylococcus epidermidis live in close proximity on human skin, and both bacterial species can be isolated from normal and acne vulgaris-affected skin sites. The antagonistic interactions between the two species are poorly understood, as well as the potential significance of bacterial interferences for the skin microbiota. Here, we performed simultaneous antagonism assays to detect inhibitory activities between multiple isolates of the two species. Selected strains were sequenced to identify the genomic basis of their antimicrobial phenotypes.
RESULTS
First, we screened 77 P. acnes strains isolated from healthy and acne-affected skin, and representing all known phylogenetic clades (I, II, and III), for their antimicrobial activities against 12 S. epidermidis isolates. One particular phylogroup (I-2) exhibited a higher antimicrobial activity than other P. acnes phylogroups. All genomes of type I-2 strains carry an island encoding the biosynthesis of a thiopeptide with possible antimicrobial activity against S. epidermidis. Second, 20 S. epidermidis isolates were examined for inhibitory activity against 25 P. acnes strains. The majority of S. epidermidis strains were able to inhibit P. acnes. Genomes of S. epidermidis strains with strong, medium and no inhibitory activities against P. acnes were sequenced. Genome comparison underlined the diversity of S. epidermidis and detected multiple clade- or strain-specific mobile genetic elements encoding a variety of functions important in antibiotic and stress resistance, biofilm formation and interbacterial competition, including bacteriocins such as epidermin. One isolate with an extraordinary antimicrobial activity against P. acnes harbors a functional ESAT-6 secretion system that might be involved in the antimicrobial activity against P. acnes via the secretion of polymorphic toxins.
CONCLUSIONS
Taken together, our study suggests that interspecies interactions could potentially jeopardize balances in the skin microbiota. In particular, S. epidermidis strains possess an arsenal of different mechanisms to inhibit P. acnes. However, if such interactions are relevant in skin disorders such as acne vulgaris remains questionable, since no difference in the antimicrobial activity against, or the sensitivity towards S. epidermidis could be detected between health- and acne-associated strains of P. acnes.
Topics: Acne Vulgaris; Antibiosis; Comparative Genomic Hybridization; DNA, Bacterial; Genome, Bacterial; Humans; Phylogeny; Propionibacterium acnes; Sequence Analysis, DNA; Skin; Staphylococcus epidermidis
PubMed: 26924200
DOI: 10.1186/s12864-016-2489-5 -
European Journal of Dermatology : EJD Feb 2021Acne vulgaris is a common pilosebaceous disease associated with Propionibacterium acnes (P. acnes). Resolution of comedones may occur in association with shrunken...
BACKGROUND
Acne vulgaris is a common pilosebaceous disease associated with Propionibacterium acnes (P. acnes). Resolution of comedones may occur in association with shrunken sebaceous glands (SGs) containing de-differentiated cells, however the role of P. acnes is unclear.
OBJECTIVES
To investigate the effects of P. acnes on aryl hydrocarbon receptor (AhR) activation, lipogenesis and differentiation in cultured immortalized human SZ95 sebocytes.
MATERIALS & METHODS
Cultured sebocytes were incubated with formalin-killed (f-) P. acnes (f-P. acnes) at different ratios of multiplicity of infection. The mRNA levels of the AhR downstream cytochrome P450 (CYP) genes were measured by quantitative RT-PCR, nuclear translocation of AhR by western blot and immunofluorescence, lipogenesis and keratinization by gene set enrichment analysis (GSEA), lipid related analysis by Oil red O staining and Nile red staining, and sebaceous differentiation-related gene expression by western blot.
RESULTS
f-P. acnes upregulated CYPs mRNA levels and induced translocation of AhR protein from the cytoplasm into the nucleus. GSEA revealed downregulation of lipogenesis and upregulation of keratinization. f-P. acnes inhibited linoleic acid-induced neutral lipid synthesis and expression of sebocyte markers, keratin 7 and mucin1/EMA, but increased expression of keratinocyte markers, keratin 10 and involucrin, which were abolished by AhR gene silencing. Inhibition of lipogenesis-related genes, such as sterol response element-binding protein, was also observed.
CONCLUSION
f-P. acnes inhibits lipogenesis and induces terminal differentiation of sebocytes, into keratinocyte-like cells, via activation of the AhR pathway in vitro, suggesting that follicular P. acnes is not only acnegenic but also promotes acne remission through feedback regulation of sebum production.
Topics: Cell Differentiation; Cells, Cultured; Formaldehyde; Humans; Propionibacterium acnes; Receptors, Aryl Hydrocarbon; Sebaceous Glands
PubMed: 33648912
DOI: 10.1684/ejd.2021.3964 -
International Journal of Dermatology Nov 2016Recent progress has steadily reported the existence of the diverse strains of Propionibacterium acnes, and these studies have contributed to the elucidation of their... (Review)
Review
Recent progress has steadily reported the existence of the diverse strains of Propionibacterium acnes, and these studies have contributed to the elucidation of their contradictory roles between normal commensals and pathogens. In this review, the authors aimed to provide an update on the recent understanding of research about P. acnes strain diversity and acne, analyzing the potential implications for clinical applications. Before the era of genomic research, P. acnes was known to be distinguished based on serological agglutination tests, cell wall sugar analysis, or fermentation traits. Since the complete genome sequence of P. acnes was first deciphered, genetic studies based on sequence data have expanded with the introduction of more refined and precise DNA-based typing methods, including multilocus sequence typing and metagenomics. These sophisticated techniques have revealed that P. acnes consists of phylogenetically distinct cluster groups with various pathogenic traits, including elicitation of inflammation, protein secretome profile, and unique distribution patterns in various skin loci. In following large-scale studies from patients' acne samples have revealed that specific sequence types are included within the phylogenetic divisions and further suggested that particular P. acnes strains play an etiologic role in acne while others are associated with health, providing a firm platform for evidential-based research into the exact role of this organism in acne. We strongly believe that future research would provide fruitful results in not only clarifying the apparent controversy with respect to roles of P. acnes but also developing therapeutic drugs by pinpointing specific targets of the pathogenic strain only.
Topics: Acne Vulgaris; Gram-Positive Bacterial Infections; Humans; Metagenomics; Multilocus Sequence Typing; Phylogeny; Propionibacterium acnes
PubMed: 27421121
DOI: 10.1111/ijd.13282