Staphylococcus aureus Biofilm Infection Compromises Wound Healing by Causing Deficiencies in Granulation Tissue...

Area of Science:

• Microbiology
• Wound Healing
• Biochemistry

Background:

• Chronic wounds often harbor bacterial infections, with Staphylococcus aureus being a prevalent species.
• Understanding the link between bacterial biofilm properties and wound pathology is crucial but challenging.
• This study investigates the pathogenic mechanisms of S. aureus biofilm in a preclinical wound model.

Purpose of the Study:

• To causatively link bacterial biofilm properties to specific pathogenic mechanisms in wound healing.
• To elucidate the role of S. aureus biofilm in collagen degradation and biomechanical compromise of wound tissue.
• To identify molecular pathways involved in S. aureus biofilm-induced wound pathology.

Main Methods:

• Utilized isogenic mutant strains of S. aureus with varying biofilm-forming abilities (ΔrexB > USA300 > ΔsarA).
• Infected full-thickness porcine cutaneous wounds with these S. aureus strains in a preclinical model.
• Assessed wound biofilm burden, collagen degradation (specifically Collagen 1), microRNA expression (miR-143), matrix metalloproteinase-2 (MMP-2) levels, and biomechanical properties (tensile strength).

Main Results:

• Higher biofilm burden was observed with ΔrexB and USA300 strains compared to ΔsarA.
• Biofilm infection led to degradation of Collagen 1 and a decreased Collagen 1/Collagen 3 ratio.
• Wound-edge miR-143 was repressed, causing upregulation of MMP-2, a collagenolytic enzyme, compromising tissue biomechanics and tensile strength.

Conclusions:

• Chronic S. aureus biofilm infection impairs granulation tissue collagen, leading to compromised wound tissue biomechanics.
• The observed tissue compromise increases the likelihood of wound recurrence (recidivism).
• This study provides critical insights into the pathogenic mechanisms of S. aureus biofilms in chronic wounds.