Targeted Prevention or Treatment of Bacterial Biofilm Infections of Severe Burns and Wounds
Abstract
Persistent infection of severe wounds, and burns in particular, represents a significant cause of deployment-related morbidity and mortality. Inability to successfully treat wound and burn infections relates to the capacity of the bacteria to form a biofilm1. In patients with severe burns, 75% of deaths will occur from sepsis or infectious complications, with P. aeruginosa accounting for over half of all burn infections. In the setting of thermal injury, an intense inflammatory response is universally present, culminating in massive recruitment of neutrophils to the tissue1. In both thermal and reperfusion injury, vascular spasm and impaired blood flow to the site is followed by reperfusion and vascular leak. Importantly, this tissue injury uncovers self antigens on the nonmuscle myosin heavy chain II (NMHC-II) that are recognized by a specific natural IgM subclass (IgMCM-22), as an early response of the innate immunity (Figure 1). Binding of IgMCM-22 to NMHC-II triggers the complement cascade, and the subsequent recruitment of neutrophils to the site of injury. Systemic or local administration of a 12-mer synthetic peptide (N2) analogous to NMHC-II is capable of binding and competitively inhibiting IgMCM-22, thus greatly reducing inflammation at the site of the wound2. Excessive neutrophil accumulation, combined with impaired clearance of the dead and dying cells, is clearly linked to tissue damage. However, recent reports have demonstrated that neutrophil products can accelerate P. aeruginosa biofilm formation. As neutrophils undergo necrosis, long strands of DNA and F-actin are released into the inflammatory milieu, and polymerize through covalent attraction. Recently it was reported that P. aeruginosa can exploit the neutrophil-rich environment by utilizing these polymers as a scaffolding, significantly enhancing early biofilm formation.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2011
- Accession Number
- ADA544414
Entities
People
- Jerry Nick
Organizations
- National Jewish Health