Transcriptomic identification of genes expressed in invasive S. aureus diabetic foot ulcer infection

Frontiers in Cellular and Infection Microbiology

Cellular and Infection Microbiology

Francis Y. Lee¹  Irvin Oh¹  Taiwo Samuel Agidigbi¹  Hyuk-Kwon Kwon²  Dejian Zhao³  James R. Knight³ 

[1] Department of Orthopedics and Rehabilitation, Yale School of Medicine, New Haven, CT, United States;Department of Orthopedics and Rehabilitation, Yale School of Medicine, New Haven, CT, United States;Division of Life Science, Gyeongsang National University, Jinju, Republic of Korea;Yale Center for Genome Analysis, Department of Genetics, Yale School of Medicine, New Haven, CT, United States;

关键词: DFU;    S. aureus;    transcriptome;    PBMC;    wound healing;    host-immunity;   

DOI  :  10.3389/fcimb.2023.1198115

 received in 2023-04-03, accepted in 2023-05-25,  发布年份 2023

来源: Frontiers

【 摘 要 】

IntroductionInfection in diabetic foot ulcers (DFUs) is one of the major complications associated with patients with diabetes. Staphylococcus aureus is the most common offending pathogen in patients with infected DFU. Previous studies have suggested the 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 may 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.MethodsThis study compared the transcriptome profile of 21 patients with S. 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 of IGHG1, IGHG2, IGHG3, IGLV3-21, and IGLV6-57 was noted during active infection at 0 weeks compared with that at 8 weeks. Lysine- and arginine-rich histones (HIST1H2AJ, HIST1H2AL, HIST1H2BM, HIST1H3B, and HIST1H3G) were upregulated at the initial phase of active infection at 0 weeks. CD177 and RRM2 were 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, and HSP90B1) 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.

【 授权许可】

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Copyright © 2023 Agidigbi, Kwon, Knight, Zhao, Lee and Oh