IntroductionInfection in diabetic foot ulcers (DFUs) is one of the major complications associated with patients with diabetes.Staphylococcus aureusis the most common offending pathogen in patients with infected DFU. Previous studies have suggested the application of species-specific antibodies againstS. aureusfor 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 may suggest potential intervention options to promote healing infected DFUs. We sought to investigate evolving host transcriptome associated with surgical treatment ofS. aureus– infected DFU.MethodsThis study compared the transcriptome profile of 21 patients withS. aureus– infected DFU who underwent initial foot salvage therapy with irrigation and debridement followed by intravenous antibiotic therapy. Blood samples were collected at the recruitment (0 weeks) and 8 weeks after therapy to isolate peripheral blood mononuclear cells (PBMCs). We analyzed the PBMC expression of transcriptomes at two different time points (0 versus 8 weeks). Subjects were further divided into two groups at 8 weeks: healed (n = 17, 80.95%) versus non-healed (n = 4, 19.05%) based on the wound healing status. DESeq2 differential gene analysis was performed.Results and discussionAn increased expression ofIGHG1,IGHG2,IGHG3,IGLV3-21, andIGLV6-57was noted during active infection at 0 weeks compared with that at 8 weeks. Lysine- and arginine-rich histones (HIST1H2AJ,HIST1H2AL,HIST1H2BM,HIST1H3B, andHIST1H3G) were upregulated at the initial phase of active infection at 0 weeks.CD177andRRM2were also upregulated at the initial phase of active infection (0 weeks) compared with that at 8 weeks of follow-up. Genes of heat shock protein members (HSPA1A,HSPE1, andHSP90B1) were high in not healed patients compared with that in healed patients 8 weeks after therapy. The outcome of our study suggests that the identification of genes evolution based on a transcriptomic profiling could be a useful tool for diagnosing infection and assessing severity and host immune response to therapies.