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Transcriptomic Identification of Genes expressed in Invasive S. aureus Diabetes Foot Ulcer infection

ABSTRACT: Transcriptomic Identification of Genes expressed in Invasive S. aureus Diabetes Foot Ulcer infection

PROVIDER: PRJNA961119 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR24288524_1.fastq.gz	Fastqsanger.gz
	SRR24288524_2.fastq.gz	Fastqsanger.gz
	SRR24288525_1.fastq.gz	Fastqsanger.gz
	SRR24288525_2.fastq.gz	Fastqsanger.gz
	SRR24288526_1.fastq.gz	Fastqsanger.gz

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Project description:Infection in diabetic foot ulcers (DFU) are one of the major complications associated with diabetic patients. Staphylococcus aureus is the most common offending pathogen in patients with infected DFU. Previous studies have suggested application of species-specific antibodies against S. aureus for diagnosis and monitoring treatment response. Early and accurate identification of the main pathogen is critical for management of DFU infection. Understanding the host immune response against species-specific infection may facilitate diagnosis and suggest potential intervention options to promote healing infected DFUs. We sought to investigate evolving host transcriptome associated with surgical treatment of S. aureus infected DFU. This study compared the transcriptome profile of twenty-one patients with S. aureus infected DFU who underwent initial foot salvage therapy with irrigation and debridement followed by intravenous antibiotics therapy. Blood samples were collected at the recruitment (0-weeks) and 8-week after therapy to isolate peripheral blood mononuclear cells (PBMC). We analyzed the PBMCs expression of transcriptomes at two different time points (0 vs 8-week). Subjects were further divided into two groups at 8-week: healed (n=17, 80.95%) versus non-healed (n=4,19.05%) based on the wound healing status. DESeq2 differential gene analysis was performed. An increased expression of IGHG1, IGHG2, IGHG3 and IGLV3-21, IGLV6-57 were noted during active infection at 0-week compared to 8-week. Lysine and arginine-rich histones (HIST1H2AJ, HIST1H2AL, HIST1H2BM, HIST1H3B and HIST1H3G) were upregulated at the initial phase of active infection at 0-week. CD177 and RRM2 were also upregulated at the initial phase of active infection (0-week) compared to 8-week follow-up. Genes of heat shock protein members (HSPA1A, HSPE1, and HSP90B1) were high in not-healed compared to healed patients 8-week after therapy. The outcome of our study suggests that identification of genes evolution based on a transcriptomic profiling could be a useful tool for diagnosing infection, assessing severity and assess host-immune response to therapies.

Project description:To analyze the gene expression of human gastric epithelial cells (GES-1) regulated by paeonifl or in based on transcript tome sequencing; to identify and analyze key genes; to study the mechanism of paeoniflorin on Leuk-1cells; and to explore its medicinal value. Method: Different doses of Ulcer-healing Decoction were used to treat GES-1, and its activity was assessed by MTT assay. Transcriptome sequencing analysis was then performed to identify differentially expressed genes (DEGs). The function and pathways of the DEGs were annotated using GO and KEGG enrichment analysis. Result: The survival rate of GES-1 cells was significantly increased under different concentrations of ulcer-healing decoction intervention (P < 0.05 or P < 0.01). After 24 hours of treatment with 80 µ g/mL ulcer-healing decoction, a total of 312 crucial DEGs were observed in GES-1 cells, of which 233 DEGs were upregulated and 79 DEGs were downregulated. The top five differentially expressed genes include CYP1A1, IL24, IKBKGP1, GDF15, SCUBE1 and OASL, ADAMTS5, SULF1, ID2, and DDX60. The functions of these genes are mainly related to promoting wound,cell proliferation and migration,immunity and inflammation.GO enrichment analysis showed that the DEGs were significantly enriched in the extracellular region and involved in biological processes such as cytokine production and response, stimulus response, and exerting molecular functions such as proliferation factor receptor activity. KEGG pathway enrichment showed that the DEGs were significantly enriched in various signaling pathways. Immunohistochemistry and other methods were used to detect differentially expressed proteins in GES-1 cells induced by ulcer-healing decoction, and the results were consistent with those from RNA-seq, thereby validating the accuracy of sequencing technologies. Conclusion: The role of ulcer-healing decoction in GES-1 is primarily reflected in regulating inflammatory factors and growth factors, promoting cell proliferation, and supporting the regeneration and repair of gastric mucosal epithelial cells.

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Transcriptomic Identification of Genes expressed in Invasive S. aureus Diabetes Foot Ulcer infection

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