Cutaneous Burn Injury Promotes Shifts in the Bacterial Microbiome in Autologous Donor Skin: Implications for Skin Grafting Outcomes

INTRODUCTION: The cutaneous microbiome maintains skin barrier function, regulates inflammation, and stimulates wound-healing responses. Burn injury promotes an excessive activation of the cutaneous and systemic immune response directed against commensal and invading pathogens. Skin grafting is the primary method of reconstructing full-thickness burns, and wound infection continues to be a significant complication. METHODS: In this study, the cutaneous bacterial microbiome was evaluated and subsequently compared to patient outcomes. Three different full-thickness skin specimens were assessed: control skin from non-burned subjects; burn margin from burn patients; and autologous donor skin from the same cohort of burn patients. RESULTS: We observed that skin bacterial community structure of burn patients was significantly altered compared with control patients. We determined that the unburned autologous donor skin from burn patients exhibits a microbiome similar to that of the burn margin, rather than unburned controls, and that changes in the cutaneous microbiome statistically correlate with several post-burn complications. We established that Corynebacterium positively correlated with burn wound infection, while Staphylococcus and Propionibacterium negatively correlated with burn wound infection. Both Corynebacterium and Enterococcus negatively correlated with the development of sepsis. CONCLUSIONS: This study identifies distinct differences in the cutaneous microbiome between burn subjects and unburned controls, and ascertains that select bacterial taxa significantly correlate with several comorbid complications of burn injury. These preliminary data suggest that grafting donor skin exhibiting bacterial dysbiosis may augment infection and/or graft failure and sets the foundation for more in-depth and mechanistic analyses in presumably "healthy" donor skin from patients requiring skin grafting procedures

Cutaneous Burn Injury Modulates Urinary Antimicrobial Peptide Responses and the Urinary Microbiome

OBJECTIVES: Characterization of urinary bacterial microbiome and antimicrobial peptides after burn injury to identify potential mechanisms leading to urinary tract infections and associated morbidities in burn patients. DESIGN: Retrospective cohort study using human urine from control and burn subjects. SETTING: University research laboratory. PATIENTS: Burn patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Urine samples from catheterized burn patients were collected hourly for up to 40 hours. Control urine was collected from "healthy" volunteers. The urinary bacterial microbiome and antimicrobial peptide levels and activity were compared with patient outcomes. We observed a significant increase in urinary microbial diversity in burn patients versus controls, which positively correlated with a larger percent burn and with the development of urinary tract infection and sepsis postadmission, regardless of age or gender. Urinary psoriasin and β-defensin antimicrobial peptide levels were significantly reduced in burn patients at 1 and 40 hours postadmission. We observed a shift in antimicrobial peptide hydrophobicity and activity between control and burn patients when urinary fractions were tested against Escherichia coli and Enterococcus faecalis urinary tract infection isolates. Furthermore, the antimicrobial peptide activity in burn patients was more effective against E. coli than E. faecalis. Urinary tract infection-positive burn patients with altered urinary antimicrobial peptide activity developed either an E. faecalis or Pseudomonas aeruginosa urinary tract infection, suggesting a role for urinary antimicrobial peptides in susceptibility to select uropathogens. CONCLUSIONS: Our data reveal potential links for urinary tract infection development and several morbidities in burn patients through alterations in the urinary microbiome and antimicrobial peptides. Overall, this study supports the concept that early assessment of urinary antimicrobial peptide responses and the bacterial microbiome may be used to predict susceptibility to urinary tract infections and sepsis in burn patients

A genomic storm in critically injured humans

Critical injury in humans induces a genomic storm with simultaneous changes in expression of innate and adaptive immunity genes

C/EBPα and C/EBPβ binding proteins modulate hepatocyte apoptosis through iNOS signaling pathway

AbstractInducible nitric oxide synthase (iNOS) and nitric oxide (NO) involve many pathophysiologic conditions. The expression of iNOS is regulated at multiple stages. Presently, the regulatory details of iNOS signaling are still unclear. This study aimed to investigate the regulatory role of C/EBPα and C/EBPβ in iNOS signaling pathway. By employing the techniques such as EMSA, ChIP assay, site-directed mutagenesis, and siRNA silencing, the relationship between iNOS and C/EBPα/C/EBPβ in rat hepatocytes was clarified. iNOS promoter was the direct transcriptional targets of the C/EBPα, C/EBPβ, and NF-κB binding proteins. There was the interactive influence between NF-κB and C/EBPα/C/EBPβ. The expression of iNOS was modulated by C/EBPα/C/EBPβ transcription factors. Moreover, the iNOS expression mediated glycochenodeoxycholate (GCDC)-induced apoptosis in hepatocytes. C/EBPα/C/EBPβ binding proteins could affect the GCDC-induced apoptosis through iNOS cascade. These findings indicate that C/EBPα and C/EBPβ regulate the iNOS expression, which may further modify cell responses such as apoptosis and cell survival