Abstract:
Antimicrobial peptides (AMPs) have attracted considerable attention because of their multiple and complex mechanisms of action toward resistant bacteria. However, reports have increasingly highlighted how bacteria can escape AMP administration. Here, we have described the use of multiple strategies including genetic and Joker algorithms as well as an artificial intelligence strategy to design bioinspired AMPs derived from bacteria, plants, and animals. This approach yielded different peptide classes including those that possess an unusually high proportion of cationic residues and hydrophobic counterparts. At least dozens of peptides emerged as prototype AMP, among natural analogs screened for their activity against an engineered luminescent Pseudomonas strain. Peptides were further characterized in terms of structure, activity, mechanism of action, and biotechnological potential for the development of new compounds useful for human and animal health. Most of those novel peptides were unstructured in water and underwent a coil-to-helix transition in hydrophobic environments. This conformation was corroborated by NMR analysis in dodecylphosphocholine micelles, which revealed an α-helical structure. Peptides generated caused a bactericidal effect at low micromolar concentrations to several resistant bacteria, causing membrane disruption, without triggering depolarization but rather hyperpolarization. Finally, here the strategies for production on a large scale were also discussed to prepare such peptides for the market. In summary, the present work presents a computational approach to explore natural products for the design of short and potent peptide antibiotics that could be used against resistant bacteria.

Bio:
Octávio Luiz Franco holds a degree in Biological Sciences from the Federal University of Ceará (1998) and a PhD in Biological Sciences (Molecular Biology) from the University of Brasília (2001). He conducted his initial post-doctoral research in 2001 at Embrapa, followed by another at the University of Edinburgh in Scotland. He has undertaken work missions in numerous countries, including Australia, Israel, Portugal, Cuba, the Netherlands, and others. Dr. Franco completed his first sabbatical at the University of Wisconsin (USA) and the second at the University of British Columbia (Canada), focusing on infectious disease control. Currently, he serves as a professor at Universidade Catolica de Brasilia and University Catolica Dom Bosco. Additionally, he coordinates the National Institute of Science and Technology Bioinspir for bioinspired products. Dr. Franco holds the position of Researcher 1A and serves as a consultant to the National Council for Scientific and Technological Development (CNPq). Furthermore, he is a member of the Brazilian Society of Biochemistry and Molecular Biology (SBBq), The American Society for Biochemistry and Molecular Biology (ASBMB), ASM (American Society of Microbiology), and the American Association for the Advancement of Science (AAAS). His research is concentrated on the development of bioproducts and bioprocesses, with a particular emphasis on the control of pathogenic microorganisms. Dr. Franco has authored nearly 500 papers, advised hundreds of students, and held dozens of patents for products that have entered the cosmetic and animal health markets.