Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Engineered skin microbiome-assisted delivery to the pilosebaceous unit

ABSTRACT: Microbes are fascinating molecular machines which can be equipped with synthetic genetic programs that allow them to produce therapeutic molecules targeted on demand upon disease sensing. Cutibacterium acnes engraftment capacity and its living habitat close to important pharmacological targets makes it an attractive chassis to create skin-delivered therapeutics. Here, we report the engineering of this bacterium, the most abundant commensal of the human skin, to produce and secrete the therapeutic molecule neutrophil gelatinase-associated lipocalin in vivo, known to modulate cutaneous sebum production.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Eduard Sabidó

LAB HEAD: Eduard Sabido

PROVIDER: PXD044802 | Pride | 2023-11-10

REPOSITORIES: Pride

ACCESS DATA

Json Xml

Similar Datasets

Molecular typing and functional profiling of acne-derived Cutibacterium acnes isolates reveal determinants of skin inflammation

Project description:Cutibacterium acnes (C. acnes) is a ubiquitous skin commensal bacterium that is generally well tolerated by the immune system. Different strain-types of C. acnes have been reported to be enriched on patients with acne. To understand if these strain-types contribute to skin inflammation, we generated a library of over 200 C. acnes isolates from skin swabs of healthy and acne subjects and assessed their strain-level identity and inflammatory potential. Phylotype II K-type strains were more frequent on healthy and acne non-lesional skin compared to lesional. Phylotype IA-1 C-type strains were dominant on acne lesional skin but absent from healthy. Measurement of host cytokine responses from C. acnes supernatant revealed neither strain-type nor skin-type association predicted inflammatory potential. However, differential proinflammatory responses were induced from identical strain-types, but these differences were not attributable to protease, short chain fatty acid or porphyrin production. Instead, whole genome sequencing revealed the presence of a linear plasmid in high inflammatory strain-types. Intradermal injection of C. acnes in mouse skin revealed a plasmid-associated inflammatory response in dermal fibroblasts, revealed by single-cell RNA sequencing. We conclude that C. acnes strain-type is not sufficient to predict inflammation but other virulence factors including a plasmid may contribute to disease.

2023-08-18 | GSE211279 | GEO

Antimicrobial production by perifollicular dermal preadipocytes is essential to the pathophysiology of acne

Project description:Innate immune defense against deep tissue infection by Staphylococcus aureus is orchestrated by fibroblasts that become antimicrobial when triggered to differentiate into adipocytes. However, the role of this process in non-infectious human diseases is unknown. To investigate the potential role of adipogenesis by dermal fibroblasts in acne, a disorder triggered by Cutibacterium acnes (C. acnes), single-cell RNA-sequencing was performed on human acne lesions and mouse skin challenged by C. acnes. A transcriptome consistent with adipogenesis was observed within specific fibroblast subsets from human acne and mouse skin lesions infected with C. acnes. Perifollicular dermal preadipocytes in human acne and mouse skin lesions showed colocalization of PREF1, an early marker of adipogenesis, and cathelicidin (Camp), an antimicrobial peptide. This capacity of C. acnes to trigger production of cathelicidin in preadipocytes was dependent on TLR2. Treatment of wild-type mice with retinoic acid (RA) suppressed the capacity of C. acnes to form acne-like lesions, inhibited adipogenesis and enhanced cathelicidin expression in preadipocytes, but lesions were unresponsive in Camp-/- mice, despite the anti-adipogenic action of RA. Analysis of inflamed skin of acne patients after retinoid treatment also showed enhanced induction of cathelicidin, a previously unknown beneficial effect of retinoids in difficult-to-treat acne. Overall, these data provide evidence that adipogenic fibroblasts are a critical component of the pathogenesis of acne and represent a potential target for future therapy.

2022-01-16 | GSE193584 | GEO

proteomic analysis of membrane vesicles from clinical Cutibacterium acnes isolates

Project description:Recently the membrane vesicles (MVs) production has been observed in Gram-positive bacterium, Cutibacterium acnes (C. acnes). In order to explore the mechanism of antibiotic resistance and the virulent components within the C. acnes-derived MVs, we isolated MVs from the clinical C. acnes, which were sensitive or resistant to antibiotics erythromycin and clindamycin. With the LC-MS/MS method, we detected several lipases, virulent factors and cell division protein differentially expressed between the sensitive and the resistant C. acnes-derived MVs.

2022-05-20 | PXD025460 | Pride

Characterization of the genes that were regulated by feeding with C. acnes strains

Project description:In the present study, we investigated the effect of Cutibacterium acnes on lifespan and susceptibility to infection with Staphylococcus aureus using Caenorhabditis elegans as a model animal. When adult C. elegans were fed C. acnes strains, the lifespan of the animals fed pathogenic C. acnes strain (HM-122) was significantly shorter than that of animals fed OP50 (control). In contrast, the lifespan of the animals fed commensal C. acnes strain (HM-555) was not significantly different from that of animals in the control group. Moreover, the worms fed the commensal C. acnes strain were more resistant to infection with S. aureus. Transcriptional profiling comparing HM-122-, HM-555- and control-fed animals suggested that genes related to “cuticle development involved in collagen and cuticulin-based cuticle molting cycle” were regulated by HM-122, and genes related to “defense response to gram-positive bacterium” were regulated by HM-555.

2021-10-07 | GSE176406 | GEO

Cutibacterium acnes subsp. acnes

Project description:Cutibacterium acnes subsp. acnes Assembly

| PRJNA319119 | ENA

Cutibacterium acnes strain:TP-CU389

Project description:Cutibacterium acnes genome

| PRJDB8192 | ENA

Effect of epinephrine on a proteome of Cutibacterium acnes

Project description:The importance of the impact of human hormones on commensal microbiota and microbial biofilms is established in lots of studies. In the present investigation, we studied the proteome of biofilms and planktonic cultures of skin actinobacterium Cutibacterium acnes. In our investigation, we tested the effect of epinephrine in concentrations 5 nM (normal blood level) and 5 µM (1000-fold higher) on 72 h biofilms and planktonic cultures in comparison with controls without the hormone administration. Also, we compared the samples treated with epinephrine in different concentrations. Also, we investigated the differences between planktonic cultures and biofilms and how the hormone influences those differences. The present database contains the raw data of proteins changes in their concentrations in described conditions.

2024-07-03 | PXD049410 | Pride

Potential Functionality of Cutibacterium acnes Extracellular Vesicles in Atopic Dermatitis and Acne Vulgaris: A Comparative Proteomic Analysis

Project description:Comparative analysis of Cutibacterium acnes extracellular vesicles proteomics from atopic dermatitis and acne vulgaris.

2023-06-03 | PXD042715 | iProX

Carbon source competition within a wound can significantly influence infection progression.

Project description:It is becoming increasingly apparent that commensal skin bacteria have an important role in wound healing and infection progression. However, the precise mechanisms underpinning many of these probiotic interactions remain to be fully uncovered. In this work, we demonstrate that the common skin commensal Cutibacterium acnes can limit the pathogenicity of the prevalent wound pathogen Pseudomonas aeruginosa in vivo. We show that this impact on pathogenicity is independent of any effect on growth, but occurs through a significant down regulation of the Type Three Secretion System (T3SS), the primary toxin secretion system utilized by P. aeruginosa in eukaryotic infection. We also show a down regulation in glucose acquisition systems, a known regulator of the T3SS, suggesting that glucose availability in a wound can influence infection progression. This suggests that introducing carbon source competition within the wound microenvironment may be an effective way to prevent or limit wound infection.

2024-07-03 | GSE236405 | GEO

Cutibacterium acnes strain:TP-CU411

Project description:Cutibacterium acnes TP-CU411

| PRJDB12853 | ENA