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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.

Despite the extended view of the composition of diabetic foot infections (DFIs), little is known about which transcriptionally active bacterial communities are pertinent to infection, and if any differences are associated with increased infection severity. We applied a RNA sequencing approach to analyze the composition, function, and pathogenicity of the active bacterial communities in DFIs. Taxonomic profiling of bacterial transcripts revealed the presence of 14 bacterial phyla in DFIs. The abundance of the Spiroplasma, Vibrio, and Mycoplasma were significantly different in different infection severities (P < 0.05). Mild and severe stages of infections were dominated by Staphylococcus aureus and Porphyromonas asaccharolytica, respectively. A total of 132 metabolic pathways were identified of which ribosome and thiamin being among the most highly transcribed pathways. Moreover, a total of 131 antibiotic resistance genes, primarily involved in the multidrug efflux pumps/exporters, were identified. Furthermore, iron acquisition systems (synthesize and regulation of siderophores) and pathways involved in the synthesis and regulation of cell-surface components associated with adhesion, colonization, and movement of bacterial cells were the most common virulence factors. These virulence factors may help bacteria compete for scares resources and survive the host wound proteases. Characterization of transcriptionally active bacterial communities can help to provide an understanding of the role of key pathogens in the development of DFIs. Such information can be clinically useful allowing replacement of DFIs empirical therapy with targeted treatment.