• Sashwati Roy, Suman Santra, Amitava Das, Sriteja Dixith, Mithun Sinha, Subhadip Ghatak, Nandini Ghosh, Pradipta Banerjee, Savita Khanna, Shomita Mathew-Steiner, Piya Das Ghatak, Britani N Blackstone, Heather M Powell, Valerie K Bergdall, Daniel J Wozniak, and Chandan K Sen.
• Department of Surgery, IU Health Comprehensive Wound Center, Indiana Center for Regenerative Medicine and Engineering, Indiana University School of Medicine, Indianapolis, IN.
• Ann. Surg. 2020 Jun 1; 271 (6): 1174-1185.

ObjectiveThe objective of this work was to causatively link biofilm properties of bacterial infection to specific pathogenic mechanisms in wound healing.BackgroundStaphylococcus aureus is one of the four most prevalent bacterial species identified in chronic wounds. Causatively linking wound pathology to biofilm properties of bacterial infection is challenging. Thus, isogenic mutant stains of S. aureus with varying degree of biofilm formation ability was studied in an established preclinical porcine model of wound biofilm infection.MethodsIsogenic mutant strains of S. aureus with varying degree (ΔrexB > USA300 > ΔsarA) of biofilm-forming ability were used to infect full-thickness porcine cutaneous wounds.ResultsCompared with that of ΔsarA infection, wound biofilm burden was significantly higher in response to ΔrexB or USA300 infection. Biofilm infection caused degradation of cutaneous collagen, specifically collagen 1 (Col1), with ΔrexB being most pathogenic in that regard. Biofilm infection of the wound repressed wound-edge miR-143 causing upregulation of its downstream target gene matrix metalloproteinase-2. Pathogenic rise of collagenolytic matrix metalloproteinase-2 in biofilm-infected wound-edge tissue sharply decreased collagen 1/collagen 3 ratio compromising the biomechanical properties of the repaired skin. Tensile strength of the biofilm infected skin was compromised supporting the notion that healed wounds with a history of biofilm infection are likely to recur.ConclusionThis study provides maiden evidence that chronic S. aureus biofilm infection in wounds results in impaired granulation tissue collagen leading to compromised wound tissue biomechanics. Clinically, such compromise in tissue repair is likely to increase wound recidivism.

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