This project will address the hypothesis that poor healing of many chronic wounds is due to the formation of infectious microbial biofilms. Biofilms are known to form preferentially on dead or damaged tissue and contribute to persistence because microorganisms in biofilms evade killing by antibiotics and by the host defenses. A corollary of the hypothesis is that therapies that effectively target microbial biofilms will improve healing of these wounds. The goal of this project is to develop knowledge and techniques needed to evaluate the potential utility of anti-biofilm therapies in the context of wound healing. This will be accomplished by characterizing the presence, speciation, structure, arid oxygen availability in wound biofilms (Aim #1), developing a suite of in vitro and in vivo models of chronic wound biofilm infection that simulate diverse aspects of biofilms in wounds (Aim #2), and applying these models to evaluate the efficacy and safety of several potential anti-biofilm technologies (Aim #3). The models include polymicrobial biofilms grown in laboratory systems, a keratinocyte scratch model interfaced with bacterial biofilm, a rafted organ culture model and mouse models of chronic wound infection. Success in this project depends on merging expertise from biofilm science and technology with expertise in wound healing and therefore requires a multidisciplinary team of biofilm microbiologists and engineers, dermatologists, cell biologists, and clinical collaborators. He project is innovative and high-risk in three important respects. This project involves investing in the biofilm concept by bringing in investigators who are outside the wound healing community. The marriage of microbial biofilm to tissue culture and animal wound models is innovative. And finally, some of the proposed anti-biofilm strategies are clearly high-risk. Wounds that fail to heal, such as diabetic foot ulcers, venous leg ulcers, and pressure ulcers are a major source of morbidity, mortality, and health care expenditure. Therapies that target biofilms may provide a significant improvement in the treatment of chronic wounds. Furthermore, the results of this research may impact the treatment of other biofilm-related diseases, such as osteomyelitis, endocarditis, prostatitis, otitis media, and sinusitis. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Exploratory Grants (P20)
Project #
5P20GM078445-03
Application #
7486759
Study Section
Special Emphasis Panel (ZGM1-PPBC-9 (WH))
Program Officer
Ikeda, Richard A
Project Start
2006-09-01
Project End
2010-08-31
Budget Start
2008-09-01
Budget End
2009-08-31
Support Year
3
Fiscal Year
2008
Total Cost
$674,913
Indirect Cost
Name
Montana State University - Bozeman
Department
Engineering (All Types)
Type
Schools of Engineering
DUNS #
625447982
City
Bozeman
State
MT
Country
United States
Zip Code
59717
James, Garth A; Ge Zhao, Alice; Usui, Marcia et al. (2016) Microsensor and transcriptomic signatures of oxygen depletion in biofilms associated with chronic wounds. Wound Repair Regen 24:373-83
Zhao, Ge; Usui, Marcia L; Underwood, Robert A et al. (2012) Time course study of delayed wound healing in a biofilm-challenged diabetic mouse model. Wound Repair Regen 20:342-52
Woods, J; Boegli, L; Kirker, K R et al. (2012) Development and application of a polymicrobial, in vitro, wound biofilm model. J Appl Microbiol 112:998-1006
Secor, Patrick R; Jennings, Laura K; James, Garth A et al. (2012) Phevalin (aureusimine B) production by Staphylococcus aureus biofilm and impacts on human keratinocyte gene expression. PLoS One 7:e40973
Kirker, Kelly R; James, Garth A; Fleckman, Philip et al. (2012) Differential effects of planktonic and biofilm MRSA on human fibroblasts. Wound Repair Regen 20:253-61
Secor, Patrick R; James, Garth A; Fleckman, Philip et al. (2011) Staphylococcus aureus Biofilm and Planktonic cultures differentially impact gene expression, mapk phosphorylation, and cytokine production in human keratinocytes. BMC Microbiol 11:143
Han, Anne; Zenilman, Jonathan M; Melendez, Johan H et al. (2011) The importance of a multifaceted approach to characterizing the microbial flora of chronic wounds. Wound Repair Regen 19:532-41
Agostinho, A M; Hartman, A; Lipp, C et al. (2011) An in vitro model for the growth and analysis of chronic wound MRSA biofilms. J Appl Microbiol 111:1275-82
Tavakkol, Zarry; Samuelson, Derrick; deLancey Pulcini, Elinor et al. (2010) Resident bacterial flora in the skin of C57BL/6 mice housed under SPF conditions. J Am Assoc Lab Anim Sci 49:588-91
Rickard, A H; Colacino, K R; Manton, K M et al. (2010) Production of cell-cell signalling molecules by bacteria isolated from human chronic wounds. J Appl Microbiol 108:1509-22

Showing the most recent 10 out of 14 publications