Transcriptomic Insights Into Host Response To Staphylococcus Aureus In Diabetic Versus Wild-type Mice During Early Wound Infection

PURPOSE: Wound healing is a complex process marked by four overlapping phases: hemostasis, inflammation, proliferation, and remodeling. Aberrations at any of these phases can lead to chronic, non-healing wounds. One such insult that is often seen are skin wound infections, most commonly by microbes such as Staphylococcus aureus or Pseudomonas aeruginosa. Diabetic patients are at a particular risk for wound infections as the pathophysiology of diabetes alters many infection-fighting processes. METHODS: The authors utilized bulk RNA sequencing data from wounds of wild type (WT, C57BL/6) and diabetic mice (db/db) that were inoculated with S. aureus and harvested at time points 3 days and 7 days. Data from the bulk RNA sequencing was analyzed using GSEA, GeneOntology (GO), and KEGG pathway for ontologic and pathway analysis. RESULTS: At day 3, diabetic mice exhibited downregulation of pathways involved in microbial clearance, including xenobiotic metabolism and inflammation-related pathways. By day 7, diabetic wounds demonstrated upregulation of distinct inflammatory pathways relative to WT mice, which may paradoxically prolong bacterial survival due to dysregulated host immune responses. CONCLUSION: These results taken together suggest that S. aureus may have become better equipped to survive in diabetic environments. The microenvironment seen in diabetic wounds may in some ways be favorable for S. aureus and allow it to alter host gene expresion, thereby improving its survival. Future research can evaluate RNA expression at later time points and pharmacologic agents to reinstate normal expression of these beneficial pathways. *Source: https://ps-rc.org/meeting/Program/2026/EP104.cgi*