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Scientific Reports Feb 2024The increasing prevalence of antibiotic resistance in Cutibacterium acnes (C. acnes) requires the search for alternative therapeutic strategies. Antimicrobial peptides...
The increasing prevalence of antibiotic resistance in Cutibacterium acnes (C. acnes) requires the search for alternative therapeutic strategies. Antimicrobial peptides (AMPs) offer a promising avenue for the development of new treatments targeting C. acnes. In this study, to design peptides with the specific inhibitory activity against C. acnes, we employed a deep learning pipeline with generators and classifiers, using transfer learning and pretrained protein embeddings, trained on publicly available data. To enhance the training data specific to C. acnes inhibition, we constructed a phylogenetic tree. A panel of 42 novel generated linear peptides was then synthesized and experimentally evaluated for their antimicrobial selectivity and activity. Five of them demonstrated their high potency and selectivity against C. acnes with MIC of 2-4 µg/mL. Our findings highlight the potential of these designed peptides as promising candidates for anti-acne therapeutics and demonstrate the power of computational approaches for the rational design of targeted antimicrobial peptides.
Topics: Humans; Antimicrobial Peptides; Phylogeny; Deep Learning; Anti-Infective Agents; Acne Vulgaris; Propionibacterium acnes; Anti-Bacterial Agents
PubMed: 38402320
DOI: 10.1038/s41598-024-55205-3 -
The Spine Journal : Official Journal of... Jun 2024An increasing number of research indicates an association between low-grade bacterial infections, particularly those caused by Propionibacterium acnes (P. acnes), and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
An increasing number of research indicates an association between low-grade bacterial infections, particularly those caused by Propionibacterium acnes (P. acnes), and the development of intervertebral disc degeneration (IDD). However, no previous meta-analysis has systematically assessed the risk factors for low-grade bacterial infections that cause IDD.
PURPOSE
This study reviewed the literature to evaluate the risk factors associated with low-grade bacterial infection in patients with IDD.
STUDY DESIGN
Systematic review and meta-analysis.
METHODS
The systematic literature review was conducted using the PubMed, Web of Science, Embase, and Cochrane Library databases. Eligible articles explicitly identified the risk factors for low-grade bacterial infections in IDD patients. Patient demographics and total bacterial infection rates were extracted from each study. Meta-analysis was performed using random- or fixed-effects models, with statistical analyses conducted using Review Manager (RevMan) 5.4 software.aut.
RESULTS
Thirty-three studies involving 4,109 patients were included in the meta-analysis. The overall pooled low-grade bacterial infection rate was 30% (range, 24%-37%), with P. acnes accounting for 25% (range, 19%-31%). P. acnes constituted 66.7% of bacteria-positive discs. Fourteen risk factors were identified, of which 8 were quantitatively explored. Strong evidence supported male sex (odds ratio [OR] = 2.15; 95% confidence interval [CI]=1.65-2.79; p<.00001) and Modic changes (MCs) (OR=3.59; 95% CI=1.68-7.76; p=.0009); moderate evidence of sciatica (OR=2.31; 95% CI=1.33-4.00; p=.003) and younger age (OR=-3.47; 95% CI=-6.42 to -0.53; p=.02). No evidence supported previous disc surgery, MC type, Pfirrmann grade, smoking, or diabetes being risk factors for low-grade bacterial infections in patients with IDD.
CONCLUSIONS
Current evidence highlights a significant association between IDD and low-grade bacterial infections, predominantly P. acnes being the most common causative agent. Risk factors associated with low-grade bacterial infections in IDD include male sex, MCs, sciatica, and younger age.
Topics: Humans; Intervertebral Disc Degeneration; Risk Factors; Propionibacterium acnes; Gram-Positive Bacterial Infections; Bacterial Infections
PubMed: 38365007
DOI: 10.1016/j.spinee.2024.02.001 -
Dermatology (Basel, Switzerland) 2024Darier disease is a rare inherited disease with dominant skin manifestations including keratotic papules and plaques on sebaceous and flexural areas. Secondary infection...
INTRODUCTION
Darier disease is a rare inherited disease with dominant skin manifestations including keratotic papules and plaques on sebaceous and flexural areas. Secondary infection of skin lesions is common, and Staphylococcus aureus commonly colonizes these lesions. The aim of the study was to characterize the bacterial microbiome of cutaneous Darier lesions compared to normal-looking skin and disease severity.
METHODS
All patients with a history of Darier followed up at Emek Medical Center were invited to participate in the study. Patients that did not use antibiotics in the past month and signed informed consent had four skin sites sampled with swabs: scalp, chest, axilla, and palm. All samples were analyzed for bacterial microbiome using 16S rDNA sequencing.
RESULTS
Two hundred and eighty microbiome samples obtained from lesional and non-lesional skin of the scalp, chest, axilla, and palm of 42 Darier patients were included in the analysis. The most abundant bacterial genera across all skin sites were Propionibacterium, Corynebacterium, Paracoccus, Micrococcus, and Anaerococcus. Scalp and chest lesions featured a distinct microbiome configuration that was mainly driven by an overabundance of Staphylococci species. Patients with more severe disease exhibited microbiome alterations in the chest, axilla, and palm compared with patients with only mild disease, driven by Peptoniphilus and Moryella genera in scalp and palmar lesions, respectively.
CONCLUSION
Staphylococci were significantly associated with Darier lesions and drove Darier-associated dysbiosis. Severity of the disease was associated with two other bacterial genera. Whether these associations also hold a causative role and may serve as a therapeutic target remains to be determined and requires further investigation.
Topics: Humans; Darier Disease; Male; Female; Dysbiosis; Adult; Middle Aged; Microbiota; Axilla; Skin; Corynebacterium; Young Adult; Propionibacterium; Micrococcus; Severity of Illness Index; Hand; Thorax; Scalp; Aged; Adolescent
PubMed: 38330926
DOI: 10.1159/000537714 -
Journal of Drugs in Dermatology : JDD Feb 2024Antibiotics, topical and oral, are a cornerstone in the treatment of acnes vulgaris specifically by targeting the skin bacterium Cutibacterium acnes. Billions of...
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.
Topics: Humans; Antimicrobial Stewardship; Drug Resistance, Bacterial; Acne Vulgaris; Anti-Bacterial Agents; Benzoyl Peroxide; Propionibacterium acnes
PubMed: 38306149
DOI: 10.36849/JDD.SF378969 -
Arthritis Research & Therapy Jan 2024Although cervical intervertebral disc (IVD) degeneration is closely associated with neck pain, its cause remains unclear. In this study, an animal model of cervical disc...
BACKGROUND
Although cervical intervertebral disc (IVD) degeneration is closely associated with neck pain, its cause remains unclear. In this study, an animal model of cervical disc degeneration and discogenic neck pain induced by a low concentration of Propionibacterium acnes (P. acnes-L) is investigated to explore the possible mechanisms of cervical discogenic pain.
METHODS
Cervical IVD degeneration and discitis was induced in 8-week-old male rats in C3-C6 IVDs through the anterior intervertebral puncture with intradiscal injections of low and high concentrations of P. acnes (P. acnes-L, n = 20 and P. acnes-H, n = 15) or Staphylococcus aureus (S. aureus, n = 15), compared to control (injection with PBS, n = 20). The structural changes in the cervical IVD using micro-CT, histological evaluation, and gene expression assays after MRI scans at 2 and 6 weeks post-modeling. The P. acnes-L induced IVD degeneration model was assessed for cervical spine MRI, histological degeneration, pain-like behaviors (guarding behavior and forepaw von Frey), nerve fiber growth in the IVD endplate region, and DRG TNF-α and CGRP.
RESULTS
IVD injection with P. acnes-L induced IVD degeneration with decreased IVD height and MRI T2 values. IVD injection with P. acnes-H and S. aureus both lead to discitis-like changes on T2-weighted MRI, trabecular bone remodeling on micro-CT, and osseous fusion after damage in the cartilage endplate adjacent to the injected IVD. Eventually, rats in the P. acnes-L group exhibited significant nociceptive hypersensitivity, nerve fiber ingrowth was observed in the IVD endplate region, inflammatory activity in the DRG was significantly increased compared to the control group, and the expression of the pain neurotransmitter CGRP was significantly upregulated.
CONCLUSION
P. acnes-L was validated to induce cervical IVD degeneration and discogenic pain phenotype, while P. acnes-H induced was identified to resemble septic discitis comparable to those caused by S. aureus infection.
Topics: Male; Rats; Animals; Intervertebral Disc Degeneration; Propionibacterium acnes; Discitis; Neck Pain; Calcitonin Gene-Related Peptide; Staphylococcus aureus; Intervertebral Disc; Disease Models, Animal
PubMed: 38297365
DOI: 10.1186/s13075-024-03269-x -
Radiology Jan 2024
Topics: Humans; Propionibacterium acnes; Empyema
PubMed: 38289207
DOI: 10.1148/radiol.231433 -
Journal of Cosmetic Dermatology May 2024Acne vulgaris is a widespread chronic inflammatory dermatological condition. The precise molecular and genetic mechanisms of its pathogenesis remain incompletely...
BACKGROUND
Acne vulgaris is a widespread chronic inflammatory dermatological condition. The precise molecular and genetic mechanisms of its pathogenesis remain incompletely understood. This research synthesizes existing databases, targeting a comprehensive exploration of core genetic markers.
METHODS
Gene expression datasets (GSE6475, GSE108110, and GSE53795) were retrieved from the GEO. Differentially expressed genes (DEGs) were identified using the limma package. Enrichment analyses were conducted using GSVA for pathway assessment and clusterProfiler for GO and KEGG analyses. PPI networks and immune cell infiltration were analyzed using the STRING database and ssGSEA, respectively. We investigated the correlation between hub gene biomarkers and immune cell infiltration using Spearman's rank analysis. ROC curve analysis validated the hub genes' diagnostic accuracy. miRNet, TarBase v8.0, and ChEA3 identified miRNA/transcription factor-gene interactions, while DrugBank delineated drug-gene interactions. Experiments utilized HaCaT cells stimulated with Propionibacterium acnes, treated with retinoic acid and methotrexate, and evaluated using RT-qPCR, ELISA, western blot, lentiviral transduction, CCK-8, wound-healing, and transwell assays.
RESULTS
There were 104 genes with consistent differences across the three datasets of paired acne and normal skin. Functional analyses emphasized the significant enrichment of these DEGs in immune-related pathways. PPI network analysis pinpointed hub genes PTPRC, CXCL8, ITGB2, and MMP9 as central players in acne pathogenesis. Elevated levels of specific immune cell infiltration in acne lesions corroborated the inflammatory nature of the disease. ROC curve analysis identified the acne diagnostic potential of four hub genes. Key miRNAs, particularly hsa-mir-124-3p, and central transcription factors like TFEC were noted as significant regulators. In vitro validation using HaCaT cells confirmed the upregulation of hub genes following Propionibacterium acnes exposure, while CXCL8 knockdown reduced pro-inflammatory cytokines, cell proliferation, and migration. DrugBank insights led to the exploration of retinoic acid and methotrexate, both of which mitigated gene expression upsurge and inflammatory mediator secretion.
CONCLUSION
This comprehensive study elucidated pivotal genes associated with acne pathogenesis, notably PTPRC, CXCL8, ITGB2, and MMP9. The findings underscore potential biomarkers, therapeutic targets, and the therapeutic potential of agents like retinoic acid and methotrexate. The congruence between bioinformatics and experimental validations suggests promising avenues for personalized acne treatments.
Topics: Humans; Acne Vulgaris; Computational Biology; Genetic Markers; Gene Regulatory Networks; Protein Interaction Maps; Gene Expression Profiling; Precision Medicine; Methotrexate; Tretinoin; MicroRNAs; Propionibacterium acnes; HaCaT Cells; Databases, Genetic
PubMed: 38268224
DOI: 10.1111/jocd.16152 -
Nature Reviews. Microbiology Mar 2024
Topics: Propionibacteriaceae; Skin
PubMed: 38238416
DOI: 10.1038/s41579-024-01011-7 -
Scientific Reports Jan 2024Acne vulgaris is a type of chronic skin disorder caused by Propionibacterium acnes (P. acnes). Neutrophil extrinsic traps (NETs) play key role in many types of...
Acne vulgaris is a type of chronic skin disorder caused by Propionibacterium acnes (P. acnes). Neutrophil extrinsic traps (NETs) play key role in many types of inflammatory skin diseases. Adipose-derived stem cells (ADSCs) was reported modulate immune responses and neutrophil activity. Here, we explored the potential role of ADSCs and the potential mechanism associated with neutrophil extracellular traps (NETs) in relieving acne vulgaris. In the P. acnes-infected ear skin model, histological staining was used to evaluate the inflammatory infiltration and NET formation in control, P. acnes, and P. acnes + ADSCs groups. Besides, western blot was used to detect the expression levels of cit-H3, MPO, and Nrf2 in ear tissue. In vitro, the immunofluorescence staining of MPO and cit-H3, and SYTOX green staining were performed to measure the NET formation. CCK-8 assay, EdU staining, and wound healing assay were used to detect the proliferation and migration abilities of keratinocytes. ELISA assay was utilized to detect the secretion of inflammatory cytokines. In P. acnes-infected ear skin, ADSC treatment significantly attenuated inflammation and NET formation via activating Nrf2 signaling pathway. In vitro, the conditioned medium of ADSCs reduced the formation of P. acne-induced NETs. Besides, ADSCs could inhibit that the NETs efficiently promoted the proliferation, migration, and inflammatory cytokine secretion of keratinocytes. Our study suggested that ADSCs could attenuate P. acne-related inflammation by inhibiting NET formation. This study provides a novel therapeutic perspective of ADSCs in combating acne vulgaris.
Topics: Humans; Extracellular Traps; NF-E2-Related Factor 2; Acne Vulgaris; Inflammation; Stem Cells; Propionibacterium acnes
PubMed: 38233540
DOI: 10.1038/s41598-024-51931-w -
Microbiology Spectrum Feb 2024Acne vulgaris caused by antibiotic-resistant () infection is difficult to treat conventionally. Phages have been suggested as a potential solution, but research on the...
Acne vulgaris caused by antibiotic-resistant () infection is difficult to treat conventionally. Phages have been suggested as a potential solution, but research on the mechanism of phage treatment is inadequate. This research investigates the underlying molecular mechanisms of phage φPaP11-13 attenuating -induced inflammation in rat models. We found that rats infected with had higher average ear thickness, greater enrichment of inflammatory cells as shown by hematoxylin-eosin (HE) staining, and fewer TUNEL (TdT-mediated dUTP Nick-End Labeling)-positive keratinocytes visualized by IF staining. Moreover, an increase of IGF-1 and IGF-1 receptor (IGF-1r) was detected using the immunohistochemical (IHC) staining method, Western blot (WB), and quantitative real-time PCR (qRT-PCR) when infected with , which was decreased after the application of phage φPaP11-13. By applying the IGF-1 antibody, it was demonstrated that the severity of -induced inflammation was relevant to the expression of IGF-1. Through WB and qRT-PCR, activation of the PI3K/Akt pathway and a down-regulation of the BAD-mediated apoptosis pathway were discovered after infection. Subsequently, it was shown that the activation of the PI3K/Akt pathway against BAD-mediated apoptosis pathway was alleviated after applying phage φPaP11-13. Furthermore, applying the IGF-1r inhibitor, Pan-PI3K inhibitor, and Akt inhibitor reversed the changing trends of BAD induced by and phage φPaP11-13. This study demonstrates that one of the critical mechanisms underlying the attenuation of acne vulgaris by phage φPaP11-13 is lysing and regulating keratinocyte apoptosis via the PI3K/Akt signaling pathway.IMPORTANCE infection-induced acne vulgaris may cause severe physical and psychological prognosis. However, the overuse of antibiotics develops drug resistance, bringing challenges in treating . Bacteriophages are currently proven effective in MDR (multiple drug-resistant) , but there is a significant lack of understanding of phage therapy. This study demonstrated a novel way of curing acne vulgaris by using phages through promoting cell death of excessive keratinocytes in acne lesions by lysing . However, the regulation of this cell cycle has not been proven to be directly mediated by phages. The hint of ternary relation among "phage-bacteria-host" inspires huge interest in future phage therapy studies.
Topics: Animals; Rats; Bacteriophages; Insulin-Like Growth Factor I; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Keratinocytes; Acne Vulgaris; Propionibacterium acnes; Inflammation; Apoptosis
PubMed: 38197658
DOI: 10.1128/spectrum.02838-23