Biofilm bacteria are estimated to cause two thirds of infections in modern clinical practice. In biofilms, microorganisms are protected from killing by innate host defenses and most available antimicrobial agents, culminating in the need for device removal in many device-associated infections (e.g., prosthetic joint infection). Given the failure of antimicrobics in the management of biofilm-associated device infections, a novel and innovative therapeutic and preventive non-antimicrobial approach is needed. Such a strategy would limit emergence of conventional antimicrobial resistance, as conventional antimicrobial agents would not be needed. Such a strategy would also limit toxicity associated with systemic antimicrobial agents. The preliminary in vitro studies described in our first submission demonstrated that electrical currents of 20 to 2000

Public Health Relevance

Microorganisms in biofilms cause a wide range of human infections, and biofilm microorganisms are resistant to most antibiotics used in clinical practice. {We have shown that electrical current is active against biofilms of six types of bacteria and one type of yeast in the laboratory and against one type of bacteria in an animal model.} We hypothesize that electrical current is active against a variety of bacteria and fungi in biofilms, which we plan to test in the laboratory and in an animal model. We further hypothesize that electrical current will not only treat, but will also prevent biofilm formation, which we will also test in the laboratory and in an animal model. We will examine the mechanism of the observed effect. We will establish optimal parameters to maximize the activity of electrical current against microbial biofilms. {And finally, we will characterize adverse effects associated with delivery of electrical current using our animal model.} Results of this study will provide a rationale and supporting data for use of electrical current for prevention and treatment of implant-associated infections (especially bone and joint infections) in humans. This new strategy would overcome the resistance to traditional antibiotics of microorganisms in biofilms.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI091594-05
Application #
8828061
Study Section
Drug Discovery and Mechanisms of Antimicrobial Resistance Study Section (DDR)
Program Officer
Huntley, Clayton C
Project Start
2011-05-01
Project End
2017-04-30
Budget Start
2015-05-01
Budget End
2017-04-30
Support Year
5
Fiscal Year
2015
Total Cost
Indirect Cost
Name
Mayo Clinic, Rochester
Department
Type
DUNS #
006471700
City
Rochester
State
MN
Country
United States
Zip Code
55905
Wi, Yu Mi; Patel, Robin (2018) Understanding Biofilms and Novel Approaches to the Diagnosis, Prevention, and Treatment of Medical Device-Associated Infections. Infect Dis Clin North Am 32:915-929
Perez, Kimberly; Patel, Robin (2018) Survival of Staphylococcus epidermidis in Fibroblasts and Osteoblasts. Infect Immun :
Schmidt-Malan, Suzannah M; Brinkman, Cassandra L; Greenwood-Quaintance, Kerryl E et al. (2018) Activity of fixed direct electrical current in experimental Staphylococcus aureus foreign-body osteomyelitis. Diagn Microbiol Infect Dis :
Peel, Trisha N; Sedarski, John A; Dylla, Brenda L et al. (2017) Laboratory Workflow Analysis of Culture of Periprosthetic Tissues in Blood Culture Bottles. J Clin Microbiol 55:2817-2826
Peel, Trisha N; Spelman, Tim; Dylla, Brenda L et al. (2017) Optimal Periprosthetic Tissue Specimen Number for Diagnosis of Prosthetic Joint Infection. J Clin Microbiol 55:234-243
Schmidt-Malan, Suzannah M; Brinkman, Cassandra L; Greenwood-Quaintance, Kerryl E et al. (2017) Activity of Electrical Current in Experimental Propionibacterium acnes Foreign-Body Osteomyelitis. Antimicrob Agents Chemother 61:
Wang, X; Greenwood-Quaintance, K E; Karau, M J et al. (2017) Ureaplasma parvum causes hyperammonemia in a pharmacologically immunocompromised murine model. Eur J Clin Microbiol Infect Dis 36:517-522
Ruiz-Ruigomez, Maria; Badiola, Jon; Schmidt-Malan, Suzannah M et al. (2016) Direct Electrical Current Reduces Bacterial and Yeast Biofilm Formation. Int J Bacteriol 2016:9727810
Thoendel, Matthew; Jeraldo, Patricio R; Greenwood-Quaintance, Kerryl E et al. (2016) Comparison of microbial DNA enrichment tools for metagenomic whole genome sequencing. J Microbiol Methods 127:141-145
Brinkman, Cassandra L; Schmidt-Malan, Suzannah M; Karau, Melissa J et al. (2016) Exposure of Bacterial Biofilms to Electrical Current Leads to Cell Death Mediated in Part by Reactive Oxygen Species. PLoS One 11:e0168595

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