This application seeks to address the impact of bacterial colonization and persistence in chronic wounds. The formation of biofilms has clearly been linked to chronic and persistent bacterial infections. This considerably delays and complicates wound healing. Unlike acute bacterial infections, which are often cleared by the host, biofilm-related chronic infections are not easily resolved even with high dose antibiotics and intact immunity. The bacterial pathogens Pseudomonas aeruginosa and Staphylococcus aureus, which are the focus of this application, cause an array of biofilm-related clinical diseases including persistent airway infections, burn wound infections, endocarditis, and surgical site infections. Unresolved infected wounds also contribute to nosocomial persistence and the spread of bacteria in health care settings. The abundance and persistence of chronic infections due to biofilm formation has led to the hypothesis that biofilms deploy directed mechanisms to subvert recognition, activation, and functions of the host immune system. This proposal will use state-of-the- art molecular and genomic approaches to better understand the impact of bacterial colonization in chronic wounds.
Aim 1 will define mechanisms by which P. aeruginosa and S. aureus resist killing by host-derived antimicrobials and innate immune cells.
Aim 2 will utilize a newly developed porcine full thickness burn chronic wound model and explanted human tissue from burn wound debridement to investigate biofilm persistent infections caused by P. aeruginosa and S. aureus. The development of a chronic infection model that can be sampled over time as well as access to materials derived from humans suffering burn-wound injury provides a relevant, unique, and novel approach for examining the effects of biofilm formation in the host. Conclusions made from in vitro data will be efficiently tested in the porcine model and human tissue for applicability in clinical infection. Ultimately information gathered will aid the treatment of an array of chronic infections including highly prevalent persistent wound infections.

Public Health Relevance

Pseudomonas aeruginosa and Staphylococcus aureus are versatile opportunistic pathogens that can cause devastating persistent wound infections. Within the wound, these organisms transform into a resistant community called a biofilm. Biofilm-related chronic infections are not easily resolved even with high dose antibiotics and intact immunity. This application will use molecular and genomic approaches to define how biofilm-growing bacteria resist antibiotics and host immune cells. This will allow us to better understand the impact of bacterial colonization in chronic wounds and aid future management and treatment of chronic infections that significantly impact human health.

Agency
National Institute of Health (NIH)
Institute
National Institute of Nursing Research (NINR)
Type
Research Project (R01)
Project #
5R01NR013898-03
Application #
8686628
Study Section
Special Emphasis Panel (ZNR1)
Program Officer
Tully, Lois
Project Start
2012-09-01
Project End
2017-06-30
Budget Start
2014-07-01
Budget End
2015-06-30
Support Year
3
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Ohio State University
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
City
Columbus
State
OH
Country
United States
Zip Code
43210
Das Ghatak, Piya; Mathew-Steiner, Shomita S; Pandey, Priyanka et al. (2018) A surfactant polymer dressing potentiates antimicrobial efficacy in biofilm disruption. Sci Rep 8:873
Pestrak, Matthew J; Chaney, Sarah B; Eggleston, Heather C et al. (2018) Pseudomonas aeruginosa rugose small-colony variants evade host clearance, are hyper-inflammatory, and persist in multiple host environments. PLoS Pathog 14:e1006842
Sinha, Mithun; Sen, Chandan K; Singh, Kanhaiya et al. (2018) Direct conversion of injury-site myeloid cells to fibroblast-like cells of granulation tissue. Nat Commun 9:936
Li, Jilong; Ghatak, Subhadip; El Masry, Mohamed S et al. (2018) Topical Lyophilized Targeted Lipid Nanoparticles in the Restoration of Skin Barrier Function following Burn Wound. Mol Ther 26:2178-2188
Vilkhu, Ramandeep; Thio, Wesley Joo-Chen; Ghatak, Piya Das et al. (2018) Power Generation for Wearable Electronics: Designing Electrochemical Storage on Fabrics. IEEE Access 6:28945-28950
Bhattacharya, Mohini; Berends, Evelien T M; Chan, Rita et al. (2018) Staphylococcus aureus biofilms release leukocidins to elicit extracellular trap formation and evade neutrophil-mediated killing. Proc Natl Acad Sci U S A 115:7416-7421
Das, Amitava; Datta, Soma; Roche, Eric et al. (2018) Novel mechanisms of Collagenase Santyl Ointment (CSO) in wound macrophage polarization and resolution of wound inflammation. Sci Rep 8:1696
Ahmed, Noha S; Ghatak, Subhadip; El Masry, Mohamed S et al. (2017) Epidermal E-Cadherin Dependent ?-Catenin Pathway Is Phytochemical Inducible and Accelerates Anagen Hair Cycling. Mol Ther 25:2502-2512
Barki, Kasturi Ganesh; Das, Amitava; Dixith, Sriteja et al. (2017) Electric Field Based Dressing Disrupts Mixed-Species Bacterial Biofilm Infection and Restores Functional Wound Healing. Ann Surg :
Singh, Kanhaiya; Pal, Durba; Sinha, Mithun et al. (2017) Epigenetic Modification of MicroRNA-200b Contributes to Diabetic Vasculopathy. Mol Ther 25:2689-2704

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