Mixed-species biofilm compromises wound healing by disrupting epidermal barrier function.
In chronic wounds, biofilm infects host tissue for extended periods of time. This work establishes the first chronic preclinical model of wound biofilm infection aimed at addressing the long-term host response. Although biofilm-infected wounds did not show marked differences in wound closure, the repaired skin demonstrated compromised barrier function. This observation is clinically significant, because it leads to the notion that even if a biofilm infected wound is closed, as observed visually, it may be complicated by the presence of failed skin, which is likely to be infected and/or further complicated postclosure. Study of the underlying mechanisms recognized for the first time biofilm-inducible miR-146a and miR-106b in the host skin wound-edge tissue. These miRs silenced ZO-1 and ZO-2 to compromise tight junction function, resulting in leaky skin as measured by transepidermal water loss (TEWL). Intervention strategies aimed at inhibiting biofilm-inducible miRNAs may be productive in restoring the barrier function of host skin.
Comprehensive Wound Center, Davis Heart & Lung Research Institute, Centers for Regenerative Medicine and Cell Based Therapies, The Ohio State University, Columbus, OH 43220 USA.|Department of Surgery, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43220 USA.
Sashwati
S
Roy
Comprehensive Wound Center, Davis Heart & Lung Research Institute, Centers for Regenerative Medicine and Cell Based Therapies, The Ohio State University, Columbus, OH 43220 USA.|Department of Surgery, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43220 USA.
Haytham
H
Elgharably
Comprehensive Wound Center, Davis Heart & Lung Research Institute, Centers for Regenerative Medicine and Cell Based Therapies, The Ohio State University, Columbus, OH 43220 USA.|Department of Surgery, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43220 USA.
Mithun
M
Sinha
Comprehensive Wound Center, Davis Heart & Lung Research Institute, Centers for Regenerative Medicine and Cell Based Therapies, The Ohio State University, Columbus, OH 43220 USA.|Department of Surgery, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43220 USA.
Kasturi
K
Ganesh
Microbial Interface Biology, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43220 USA.|Department of Microbial Infection and Immunity, Microbiology, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43220 USA.|Deparment of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43220 USA.
Sarah
S
Chaney
Microbial Interface Biology, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43220 USA.|Department of Microbial Infection and Immunity, Microbiology, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43220 USA.
Ethan
E
Mann
Department of Surgery, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43220 USA.
Christina
C
Miller
Department of Surgery, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43220 USA.
Savita
S
Khanna
Department of Veterinary Preventive Medicine, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43220 USA.
Valerie K
VK
Bergdall
Department of Materials Science and Engineering, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43220 USA.
Heather M
HM
Powell
Department of Surgery, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43220 USA.
Charles H
CH
Cook
Comprehensive Wound Center, Davis Heart & Lung Research Institute, Centers for Regenerative Medicine and Cell Based Therapies, The Ohio State University, Columbus, OH 43220 USA.|Department of Plastic Surgery, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43220 USA.
Gayle M
GM
Gordillo
Microbial Interface Biology, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43220 USA.|Department of Microbial Infection and Immunity, Microbiology, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43220 USA.
Daniel J
DJ
Wozniak
Comprehensive Wound Center, Davis Heart & Lung Research Institute, Centers for Regenerative Medicine and Cell Based Therapies, The Ohio State University, Columbus, OH 43220 USA.
Chandan K
CK
Sen
D040981:Acinetobacter baumannii / Q000502:physiology*; D000818:Animals; D018441:Biofilms; D002463:Cell Membrane Permeability / Q000502:physiology*; D003646:Debridement; D004817:Epidermis / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000378:metabolism; D023421:Models, Animal; D011550:Pseudomonas aeruginosa / Q000502:physiology*; D012867:Skin / Q000378:metabolism; D013552:Swine; D014945:Wound Healing / Q000502:physiology*; D062826:Zonula Occludens-1 Protein / Q000378:metabolism; D062827:Zonula Occludens-2 Protein / Q000378:metabolism
D035683:MicroRNAs; C569043:Tjp1 protein, mouse; C569047:Tjp2 protein, mouse; D062826:Zonula Occludens-1 Protein; D062827:Zonula Occludens-2 Protein
microRNA; mixed-species biofilm; porcine burn wounds; transepidermal water loss (TEWL); wound biofilm