AUTHOR=Agidigbi Taiwo Samuel , Kwon Hyuk-Kwon , Knight James R. , Zhao Dejian , Lee Francis Y. , Oh Irvin 

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

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=13

YEAR=2023

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2023.1198115

DOI=10.3389/fcimb.2023.1198115

ISSN=2235-2988

ABSTRACT=<sec><title>Introduction</title><p>Infection in diabetic foot ulcers (DFUs) is one of the major complications associated with patients with diabetes. <italic>Staphylococcus aureus</italic> is the most common offending pathogen in patients with infected DFU. Previous studies have suggested the application of species-specific antibodies against <italic>S. aureus</italic> 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 <italic>S. aureus</italic>– infected DFU.</p></sec><sec><title>Methods</title><p>This study compared the transcriptome profile of 21 patients with <italic>S. aureus</italic>– 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. </p></sec><sec><title>Results and discussion</title><p>An increased expression of <italic>IGHG1</italic>, <italic>IGHG2</italic>, <italic>IGHG3</italic>, <italic>IGLV3-21</italic>, and <italic>IGLV6-57</italic> was noted during active infection at 0 weeks compared with that at 8 weeks. Lysine- and arginine-rich histones (<italic>HIST1H2AJ</italic>, <italic>HIST1H2AL</italic>, <italic>HIST1H2BM</italic>, <italic>HIST1H3B</italic>, and <italic>HIST1H3G</italic>) were upregulated at the initial phase of active infection at 0 weeks. <italic>CD177</italic> and <italic>RRM2</italic> 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 (<italic>HSPA1A</italic>, <italic>HSPE1</italic>, and <italic>HSP90B1</italic>) 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.</p></sec>