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ABSTRACT: Amplicon-based NGS to detect Cutibacterium acnes phylotypes

PROVIDER: PRJNA801471 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR17817900_1.fastq.gz	Fastqsanger.gz
	SRR17817900_2.fastq.gz	Fastqsanger.gz
	SRR17817901_1.fastq.gz	Fastqsanger.gz
	SRR17817901_2.fastq.gz	Fastqsanger.gz
	SRR17817902_1.fastq.gz	Fastqsanger.gz

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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.

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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.

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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.

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

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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.

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