Microsensor and transcriptomic signatures of oxygen depletion in biofilms associated with chronic wounds

Garth A. James; Alice Ge Zhao; Marcia Usui; Robert A. Underwood; Hung Nguyen; Haluk Beyenal; Elinor deLancey Pulcini; Alessandra Agostinho Hunt; Hans C. Bernstein; Philip Fleckman; John Olerud; Kerry S. Williamson; Michael J. Franklin; Philip S. Stewart

doi:10.1111/wrr.12401

journal article Feb 16, 2016

Microsensor and transcriptomic signatures of oxygen depletion in biofilms associated with chronic wounds

Garth A. James Alice Ge Zhao Marcia Usui Robert A. Underwood Hung Nguyen

Haluk Beyenal Elinor deLancey Pulcini Alessandra Agostinho Hunt Hans C. Bernstein Philip Fleckman John Olerud Kerry S. Williamson Michael J. Franklin Philip S. Stewart

Wound Repair and Regeneration Vol. 24 No. 2 pp. 373-383 · Wiley

View at Publisher Save 10.1111/wrr.12401

Abstract

AbstractBiofilms have been implicated in delayed wound healing, although the mechanisms by which biofilms impair wound healing are poorly understood. Many species of bacteria produce exotoxins and exoenzymes that may inhibit healing. In addition, oxygen consumption by biofilms and by the responding leukocytes, may impede wound healing by depleting the oxygen that is required for healing. In this study, oxygen microsensors to measure oxygen transects through in vitro cultured biofilms, biofilms formed in vivo within scabs from a diabetic (db/db) mouse wound model, and ex vivo human chronic wound specimens was used. The results showed that oxygen levels within mouse scabs had steep gradients that reached minima ranging from 17 to 72 mmHg on live mice and from 6.4 to 1.1 mmHg on euthanized mice. The oxygen gradients in the mouse scabs were similar to those observed for clinical isolates cultured in vitro and for human ex vivo specimens. To characterize the metabolic activities of the bacteria in the mouse scabs, transcriptomics analyses of Pseudomonas aeruginosa biofilms associated with the db/db mice wounds was performed. The results demonstrated that the bacteria expressed genes for metabolic activities associated with cell growth. Interestingly, the transcriptome results also indicated that the bacteria within the wounds experienced oxygen‐limitation stress. Among the bacterial genes that were expressed in vivo were genes associated with the Anr‐mediated hypoxia‐stress response. Other bacterial stress response genes highly expressed in vivo were genes associated with stationary‐phase growth, osmotic stress, and RpoH‐mediated heat shock stress. Overall, the results supported the hypothesis that bacterial biofilms in chronic wounds promote chronicity by contributing to the maintenance of localized low oxygen tensions, through their metabolic activities and through their recruitment of cells that consume oxygen for host defensive processes.

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Details

Published: Feb 16, 2016
Vol/Issue: 24(2)
Pages: 373-383
License: View

Authors

G

Garth A. James

Center for Biofilm Engineering Montana State University Bozeman Montana

A

Alice Ge Zhao

Division of Dermatology, Department of Medicine University of Washington Seattle Washington

M

Marcia Usui

Division of Dermatology, Department of Medicine University of Washington Seattle Washington

R

Robert A. Underwood

Division of Dermatology, Department of Medicine University of Washington Seattle Washington

H

Hung Nguyen

The Gene and Linda Voiland School of Chemical Engineering and Bioengineering Washington State University Pullman Washington

H

Haluk Beyenal

The Gene and Linda Voiland School of Chemical Engineering and Bioengineering Washington State University Pullman Washington

E

Elinor deLancey Pulcini

Center for Biofilm Engineering Montana State University Bozeman Montana

A

Alessandra Agostinho Hunt

Department of Microbiology and Molecular Genetics, 5180 Biomedical and Physical Sciences Michigan State University East Lansing Michigan

H

Hans C. Bernstein

Pacific Northwest National Laboratory, Chemical and Biological Signature Science Richland Washington

P

Philip Fleckman

Division of Dermatology, Department of Medicine University of Washington Seattle Washington

J

John Olerud

Division of Dermatology, Department of Medicine University of Washington Seattle Washington

K

Kerry S. Williamson

Center for Biofilm Engineering Montana State University Bozeman Montana

M

Michael J. Franklin

Center for Biofilm Engineering Montana State University Bozeman Montana

P

Philip S. Stewart

Center for Biofilm Engineering Montana State University Bozeman Montana

Cite This Article

Garth A. James, Alice Ge Zhao, Marcia Usui, et al. (2016). Microsensor and transcriptomic signatures of oxygen depletion in biofilms associated with chronic wounds. Wound Repair and Regeneration, 24(2), 373-383. https://doi.org/10.1111/wrr.12401

Microsensor and transcriptomic signatures of oxygen depletion in biofilms associated with chronic wounds

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