Implant medical devices are widely utilized as an essential support to patients. It is projected that many people will use at least one such device during their life time. However, there are medical issues with these devices such as bacterial infection. In particular, the formation of bacterial biofilms in implant medical devices further complicates the problem. Biofilms are bacterial communities that work together to escape the killing by the host or antibiotics. Currently, there is no treatment for such biofilms on medical devices and the last solution is to replace the infected ones. Such a replacement is costly and painful, however. Therefore, the objective of this proposal is to develop novel antimicrobial peptides and immobilization technologies that prevent bacterial biofilm formation on polymer materials of medical significance. Unlike traditional antibiotics, antimicrobial peptides remain potent after millions of years' evolution. We hypothesize that the immobilization of short antimicrobial peptides of varying activities can prevent biofilm formation on the polyethylene terephthalate (PET) surface. To test our hypothesis, we have designed the following specific aims: (1) To optimize the short antimicrobial peptide by sequence permutation; and (2) To immobilize the optimized peptide to the polyethylene terephthalate surface. We are well prepared to pursue this project. We have obtained preliminary results that support the feasibility of this research in the PI's laboratory. The anticipated outcomes of this R03 project are two fold. First, this project will lead to a family of short peptides with varying activity against superbugs. Second, the development of novel peptide immobilization technology will bring forth new possibilities to patients who are in need of new implant medical devices with improved properties. Finally, the project also provides an excellent training opportunity to the PI's postdoctoral fellow who will pursue an independent career in this direction.

Public Health Relevance

Implant medical device infection is extremely difficult to treat because of the formation of bacterial biofilms. The objective of this research project is to develop novel short antimicrobial peptides and peptide immobilization technologies that will allow us to modify the material surface to prevent biofilm formation.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Small Research Grants (R03)
Project #
5R03AI128230-02
Application #
9388956
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Xu, Zuoyu
Project Start
2016-12-01
Project End
2018-11-30
Budget Start
2017-12-01
Budget End
2018-11-30
Support Year
2
Fiscal Year
2018
Total Cost
Indirect Cost
Name
University of Nebraska Medical Center
Department
Pathology
Type
Schools of Medicine
DUNS #
168559177
City
Omaha
State
NE
Country
United States
Zip Code
68198
Mishra, Biswajit; Reiling, Scott; Zarena, D et al. (2017) Host defense antimicrobial peptides as antibiotics: design and application strategies. Curr Opin Chem Biol 38:87-96
Mishra, Biswajit; Lushnikova, Tamara; Golla, Radha M et al. (2017) Design and surface immobilization of short anti-biofilm peptides. Acta Biomater 49:316-328
Zarena, D; Mishra, Biswajit; Lushnikova, Tamara et al. (2017) The ? Configuration of the WWW Motif of a Short Trp-Rich Peptide Is Critical for Targeting Bacterial Membranes, Disrupting Preformed Biofilms, and Killing Methicillin-Resistant Staphylococcus aureus. Biochemistry 56:4039-4043