Grants and Contributions:

Grant or Award spanning more than one fiscal year (2017-2018 to 2019-2020).

With development of antibacterial resistance among numerous strains of infectious bacteria, antimicrobial peptides (AMPs) are considered to be among the best candidates to replace traditional antibiotics. AMPs are produced and employed by immune system of most organisms.x000D
Most of the naturally occurring AMPs are active against several types of infectious bacteria, but many of them are toxic to mammalians at therapeutic dosages. Use of machine learning (ML) methods, together with our current knowledge of natural AMPs, we can discover novel AMPs, with much less toxicity to mammalians and increased effectiveness against pathogens.x000D
In this project, we will use ML to develop novel AMPs, specifically for targeting the intestinal salmonella infections in pig farms. Data from previously known and studied AMPs will be used as input to the ML calculations. Within a projected two-year period for this project, we expect to deliver better antimicrobials for treating intestinal salmonella infections in pigs. AMPs discovered using ML methods will be tested in vitro for their antimicrobial activity and cytotoxicity. The secondary structure of the best candidate AMPs from this stage will be determined using nuclear magnetic resonance spectroscopy and used in atomistic molecular dynamics simulations to obtain a detailed picture of antimicrobial activity.x000D
We will examine our best candidate AMP (currently, HHC-36) for its effectiveness and resistance to proteolytic degradation through a number of in vitro tests.x000D
When administered orally to the infected animal, we require that the peptide resists to degradation by the digestive enzymes and the highly acidic environment of the stomach. We will therefore study the survival rate of the peptide as it passes through simulated intestinal track of the swine. If needed, delivery methods such as use of capsules for preserving the peptide in the pig's digestive system will also be considered and proposed for future animal trials.x000D