KSEF R&D Excellence: Expression of ANtimicrobial Peptides in Plants to Treat Human/Animal Microbial Oral Infectious Diseases

  • Ebersole, Jeffrey (PI)
  • Huang, Chifu (CoI)
  • Nagy, Peter (CoI)

Grants and Contracts Details


Anti-microbial peptides (AMPs) represent innate host defense molecules that respond to the commensal microbiota at mucosal sites, and are designed to contribute to maintenance of homeostasis between the host and the autochthonous microbial ecology at these mucosal sites (eg. oral cavity, respiratory, gastrointestinal, genitourinary tracts). These small polypeptides display hydrophobic/cationic properties and adopt an amphipathic structure, and are classified into three major groups: (i) D-helices (cecropins, magainins), (ii) cyclic with paired cysteine residues (defensins, protegrin), and (iii) an over-representation of some amino acids (proline rich, histidine rich.). This unique structure is believed to be essential for their antimicrobial actions, enabling intercalation into bacterial cell membranes creating pores and resulting in osmotic lysis. The AMPs exhibit potent/nonspecific killing of a variety of bacterial and fungal microorganisms, including oral pathogens. AMPs are constitutively expressed via continuous stimulation of the external surfaces, and can be induced by active challenge of host tissues. An innovative aspect of the use of these AMPs by our research team will be as locally delivered antimicrobials for adjunctive management of the oral infections of chronic periodontal disease, with the potential to ameliorate systemic sequelae. As natural bactericidal agents, the AMPs appear as attractive candidates for new antimicrobial strategies. However, application of AMPs to combat infectious diseases has been limited by the inability to develop large-scale production of active molecules, since they cannot be produced in prokaryotic expression systems. It is clear that production of "Plant Made Pharmaceuticals (PMP)" has become a viable technology system for biomolecules, including the use of a tobacco (Nicotinia tabacum)-based plant expression system. A plant-based production system could potentially generate large amounts of AMPs, with lower production cost and availability of a large biomass. In this research, we will use N. tabacum as an "AMP production system" to generate recombinant AMPs and document that this expression system will generate sufficient levels for potential commercialization in treating human/animal infections. We will use various bioengineering methods to express "modified AMPs" (Ie. concatenated molecules, insertion of protease cleavage sites, etc.) in order to increase the stability of the recombinant AMPs and facilitate their purification process. Key Word: antimicrobial peptides, tobacco, oral bacteria, plant-made pharmaceuticals
Effective start/end date11/1/0510/31/07


  • KY Science and Technology Co Inc: $49,999.00


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