Staphylococcus aureus Biofilm Infection Compromises Wound Healing By Causing Deficiencies In Granulation Tissue Collagen
Suman Santra1, Sashwati Roy1, Sriteja Dixith1, Amitava Das1, Subhadip Ghatak1, Piya Das Ghatak1, Savita Khanna1, Shomita Mathew-Steiner1, Valerie K. Bergdall2, Daniel J. Wozniak3, Chandan K. Sen1.
1Comprehensive Wound Center, The Ohio State University, Columbus, OH, USA, 2Department of Veterinary Preventive Medicine, The Ohio State University, Columbus, OH, USA, 3Department of Microbiology, The Ohio State University, Columbus, OH, USA.
Background- S. aureus (SA) 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 SA with varying degree of biofilm formation ability, was studied in an established pre-clinical porcine model of wound biofilm infection. Methods- Pathogenic clinically isolated S. aureus USA300LAC (USA300) was studied. The isogenic mutant strains USA300::sar A (ΔsarA) and USA300::rex B (ΔrexB) were used as hypo- and hyper-biofilm forming mutants, respectively. The biofilm forming ability of these mutants was characterized in a preclinical persistent (8 weeks) biofilm infection model. These strains were then utilized to establish varying degree of biofilm infection in wounds as an approach to causatively link wound pathology to biofilm properties of SA infection. Results- The wound biofilm burden was significantly higher in the ΔrexB and USA300 in d14 and d35 burn wound biopsies, forming thick and dense aggregates of biofilm colonization on wounds compared to ΔsarA (p˂0.05; n=6). Graded loss of collagen 1 expression was observed in response to varying degrees of SA biofilm infection (p˂0.05; n=6). Significant reduction in Col1 mRNA and protein expression were noted in USA300 and ΔrexB infected compared to the ΔsarA infected wounds. Levels of the immature collagen Col3 were higher in the granulation tissue of wounds infected with ΔrexB. miR-143 was identified as a novel biofilm sensitive miRNA which via MMP-2 induction directly downregulates wound fibroblast collagen 1 levels. Conclusion- This study provides maiden evidence that chronic SA biofilm infection in wounds results in impaired granulation tissue collagen leading to compromised wound healing. Clinically, such compromise in tissue repair is likely to increase wound recidivism.
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