Heravi Fatemah Sadeghpour, Zakrzewski Martha, Aboulkheyr Estarabadi Hamidreza, Vickery Karen, Hu Honghua
Surgical Infection Research Group, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW, Australia.
QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
Front Microbiol. 2021 Feb 4;12:613697. doi: 10.3389/fmicb.2021.613697. eCollection 2021.
The normal continuity of skin tissue can be affected by invading pathogens and lead to a series of complicated physiological events. Using an RNA sequencing-based approach, we have captured a metatranscriptomic landscape from diabetic foot infections (DFIs). The hierarchical clustering of the top 2,000 genes showed the expression of four main clusters in DFIs (A, B, C, and D). Clusters A and D were enriched in genes mainly involved in the recruitment of inflammatory cells and immune responses and clusters B and C were enriched in genes related to skin cell development and wound healing processes such as extracellular structure organization and blood vessel development. Differential expression analysis showed more than 500 differentially expressed genes (DEGs) between samples with a low number of virulence factors and samples with a high number of virulence factors. Up-regulated and down-regulated genes were mainly involved in adaptive/native immune responses and transport of mature mRNAs, respectively. Our results demonstrated the importance of inflammatory cytokines of adaptive/native immunity in the progression of DFIs and provided a useful groundwork for capturing gene snapshots in DFIs. In addition, we have provided a general introduction to the challenges and opportunities of RNA sequencing technology in the evaluation of DFIs. Pathways identified in this study such as immune chemokines, Rho GTPases, and corresponding effectors might be important therapeutic targets in the management of DFIs.
皮肤组织的正常连续性可能会受到入侵病原体的影响，并引发一系列复杂的生理事件。通过基于RNA测序的方法，我们获取了糖尿病足感染（DFIs）的宏转录组图谱。对排名前2000的基因进行层次聚类分析，结果显示DFIs中存在四个主要的基因表达簇（A、B、C和D）。A簇和D簇中主要富集了与炎症细胞募集和免疫反应相关的基因，而B簇和C簇中则富集了与皮肤细胞发育和伤口愈合过程相关的基因，如细胞外结构组织和血管发育。差异表达分析显示，在毒力因子数量少的样本和毒力因子数量多的样本之间，有超过500个差异表达基因（DEGs）。上调基因和下调基因分别主要参与适应性/天然免疫反应和成熟mRNA的转运。我们的研究结果证明了适应性/天然免疫的炎症细胞因子在DFIs进展中的重要性，并为获取DFIs中的基因快照提供了有用的基础。此外，我们还概述了RNA测序技术在评估DFIs方面面临的挑战和机遇。本研究中确定的免疫趋化因子、Rho GTP酶和相应效应器等信号通路可能是DFIs治疗中的重要靶点。
