Targeting Persister Hyperbiofilm Forming Bacterial Infection: The GelATA Wound Care Dressing

BACKGROUND: Management of chronic wounds resistant to antibiotics is a clinical challenge. Persister bacterial phenotypes such as small colony variants (SCV) are a subpopulation of antibiotic-tolerant bacterial cells that are often hyperbiofilm forming in nature. The key to managing such hostile biofilms of persister bacteria is complete eradication and one approach is to dismantle the structural framework of these biofilms. Extracellular DNA is a major component of the biofilm. DNase treatments can eradicate standard biofilms but not persister biofilms. Our work showed that, fragmented extracellular DNA (eDNA) released from a persister strain of Pseudomonas aeruginosa (PAO1ΔwspF) biofilm was responsible for resistance to disruption by DNase. PAO1ΔwspF biofilm can be disrupted by triammonium aurintricarboxylic acid (ATA), a chemical inhibitor of covalent binding between eDNA and protein with synergistic antimicrobial effect due to the ammonium salt. In this study, we tested the efficacy of GelATA wound care dressing (ATA incorporated into a polymer-based gel*) against polymicrobial persister biofilm infection in a preclinical porcine burn wound model.

METHODS:Eight 2”x2” full thickness burn wounds were created on the dorsum of (70-80lb) female domestic white pigs (n=4) using a standardized method published by us. Polymicrobial biofilm infection was established with clinical isolates of P.aeruginosa (PAO1 ΔwspF) and Staphylococcus aureus (S. aureus rexB). Wounds were treated with either standard of care (SOC)†dressing or GelATA once weekly. Progression of wound healing was followed using non-invasive imaging: Digital images and Trans Epidermal Water Loss (TEWL). Histopathological examination and Scanning Electron Microscopy (SEM) of the burn wounds were performed at day 56.

RESULTS:SEM imaging of GelATA treated wounds showed disrupted biofilm formation with less bacterial colonization compared to SOC treatment. Furthermore, GelATA significantly (p< 0.05) enhanced wound closure and re-epithelialization of persister biofilm-infected wounds (p< 0.05). Interestingly, improved wound closure with inhibition of biofilm formation resulted in functional healing which was evident by significant decrease in TEWL (p< 0.05) and improved skin barrier function in GelATA treated wounds.

CONCLUSIONS:This work presents first in vivo evidence for the efficacy of GelATA in disrupting persister biofilm and promoting improved wound closure, functional and as photographed, in a porcine burn wound model.