title: Staphylococcus aureus induces hypoxia and cellular damage in porcine dermal explants.
abstract: We developed a porcine dermal explant model to determine the extent to which Staphylococcus aureus biofilm communities deplete oxygen, change pH, and produce damage in underlying tissue. Microelectrode measurements demonstrated that dissolved oxygen (DO) in biofilm-free dermal tissue was 4.45 ± 1.17 mg/liter, while DO levels for biofilm-infected tissue declined sharply from the surface, with no measurable oxygen detectable in the underlying dermal tissue. Magnetic resonance imaging demonstrated that biofilm-free dermal tissue had a significantly lower relative effective diffusion coefficient (0.26 ± 0.09 to 0.30 ± 0.12) than biofilm-infected dermal tissue (0.40 ± 0.12 to 0.48 ± 0.12; P < 0.0001). Thus, the difference in DO level was attributable to biofilm-induced oxygen demand rather than changes in oxygen diffusivity. Microelectrode measures showed that pH within biofilm-infected explants was more alkaline than in biofilm-free explants (8.0 ± 0.17 versus 7.5 ± 0.15, respectively; P < 0.002). Cellular and nuclear details were lost in the infected explants, consistent with cell death. Quantitative label-free shotgun proteomics demonstrated that both proapoptotic programmed cell death protein 5 and antiapoptotic macrophage migration inhibitory factor accumulated in the infected-explant spent medium, compared with uninfected-explant spent media (1,351-fold and 58-fold, respectively), consistent with the cooccurrence of apoptosis and necrosis in the explants. Biofilm-origin proteins reflected an extracellular matrix-adapted lifestyle of S. aureus. S. aureus biofilms deplete oxygen, increase pH, and induce cell death, all factors that contribute to impede wound healing.
authors.affiliation: Paul G. Allen School for Global Animal Health, Washington State University, Pullman, Washington, USA.
authors.forename: Abdul G
authors.initials: AG
authors.lastname: Lone
authors.affiliation: School of Chemical Engineering & Bioengineering, Washington State University, Pullman, Washington, USA.
authors.forename: Erhan
authors.initials: E
authors.lastname: Atci
authors.affiliation: Environmental Molecular Sciences Laboratory, Pacific Northwest National Laboratory, Richland, Washington, USA.
authors.forename: Ryan
authors.initials: R
authors.lastname: Renslow
authors.affiliation: School of Chemical Engineering & Bioengineering, Washington State University, Pullman, Washington, USA.
authors.forename: Haluk
authors.initials: H
authors.lastname: Beyenal
authors.affiliation: Animal Disease Research Unit, Agricultural Research Service, U.S. Department of Agriculture, Pullman, Washington, USA Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, Washington, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Noh
authors.affiliation: Department of Veterinary Clinical Sciences, Institute of Biological Chemistry, Washington State University, Pullman, Washington, USA.
authors.forename: Boel
authors.initials: B
authors.lastname: Fransson
authors.affiliation: School of Chemical Engineering & Bioengineering, Washington State University, Pullman, Washington, USA.
authors.forename: Nehal
authors.initials: N
authors.lastname: Abu-Lail
authors.affiliation: Department of Veterinary Clinical Sciences, Institute of Biological Chemistry, Washington State University, Pullman, Washington, USA.
authors.forename: Jeong-Jin
authors.initials: JJ
authors.lastname: Park
authors.affiliation: Department of Veterinary Clinical Sciences, Institute of Biological Chemistry, Washington State University, Pullman, Washington, USA.
authors.forename: David R
authors.initials: DR
authors.lastname: Gang
authors.affiliation: Paul G. Allen School for Global Animal Health, Washington State University, Pullman, Washington, USA drcall@wsu.edu.
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Call
mesh_terms: D000818:Animals; D018441:Biofilms / Q000254:growth & development; D003469:Culture; D006863:Hydrogen-Ion Concentration; D010100:Oxygen / Q000378:metabolism*; D010101:Oxygen Consumption; D012867:Skin / Q000382:microbiology*; D013211:Staphylococcus aureus / Q000502:physiology*; D013552:Swine; D046509:Tissue Culture Techniques
chemical_list: D010100:Oxygen
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