Exploring Antimicrobial Peptides as Alternatives to Antibiotics

Bacterial infections are frequently treated with antibiotic drugs. However, this is becoming more difficult due to the overuse of antibiotics. Challenging virulent pathogens include Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp., collectively known as ESKAPE pathogens. Thus, physicians and researchers are seeking alternatives to antibiotics, such as antimicrobial peptides (AMPs). AMPs are peptide-based biomolecules with antibacterial properties.
In nature, AMPs are produced by a diverse set of organisms as a defense mechanism against bacterial infections. Previous research has shown that bacteria exhibit greater difficulty in developing resistance to AMPs compared to current antibiotics. At the Birol Lab, we have previously identified numerous AMPs effective against drug resistant bacteria, and our aim in this project is to conduct in vitro and in vivo tests to assess their efficacy and safety and to prioritize them for future downstream studies.
As the intern, I will determine the minimum inhibitory concentration (MIC) that inhibits the growth of bacterial pathogens for designed and optimized AMPs to assess their efficacy in vitro through antimicrobial susceptibility testing (AST). ASTs will be conducted against various bacterial pathogens, focusing on the ESKAPE pathogens. To assess the safety and toxicity of the AMPs in vitro, I will determine the concentration that lyses 50% of the red blood cells (RBCs) for each AMP in a hemolysis assay. Results of the AST and hemolysis assays will be used to prioritize the AMPs with low MICs and low toxicity to RBCs. After testing all the AMPs, I will list the best candidates for future research.
To test the safety and efficacy of the AMPs in vivo, we will conduct controlled animal experiments in collaboration with a contractual research facility. I will participate in the animal experiments and perform statistical analyses on the data generated to investigate the effects of the AMPs on model animals.
In this project, I will learn how to streak bacteria on agar plates following an aseptic protocol and conduct AST and hemolysis assays. I will also learn how to conduct data analysis on the raw results of these assays to prepare a prioritized list of AMP candidates. For the animal experiments, I will learn proper methods to prepare AMP solutions and animal handling protocols. I will learn to build an analysis pipeline using RStudio to analyze the results and conduct appropriate statistical tests on the results. At the end of the internship, I will have a solid understanding of how to conduct scientific research and how to analyze the collected data.
This project offers a strategic and cost-effective approach to advancing the industrial partner Amphoraxe’s core mission. By integrating academic expertise with the company’s industry capabilities, the initiative streamlines research and development (R&D) while optimizing resource utilization.
The project aims directly align with the company’s goal of developing novel AMPs, accelerating technology translation in life sciences. The project will generate data crucial for product development and regulatory approval. Additionally, this internship will foster talent development, creating a potential pipeline for future recruitment.
The program’s scientific outcomes have the potential to establish the company’s position as a leader in life sciences innovation. In essence, this collaborative project fosters a holistic approach to advancing Amphoraxe’s antimicrobial research program, strategically benefiting multiple aspects of the company’s operations.