Addressing antimicrobial resistance by using macrocyclic peptides
Samilla B. Rezende
A , Elizabete S. Cândido A , Ludovico Migliolo A , Marlon H. Cardoso A B * and Octávio L. Franco A C *
A
B
C
Dr Samilla Beatriz de Rezende received her PhD in biotechnology from Universidade Católica Dom Bosco. She was a visiting PhD student at the Institute for Molecular Bioscience, The University of Queensland, Australia, in Prof. David Craik’s lab, and worked with Prof. Marlon H. Cardoso’s group and Prof. Octávio Franco’s lab on antimicrobial peptides and peptidomimetics. Her research focuses on rational peptide design, bioinformatics, and structural biophysics. Moreover, she has authored 12 international journal articles, contributed to book chapters and scientific conferences, and is co-inventor of a patent. She is currently a Postdoctoral Research Fellow in the MICRO Lab at the University of Alberta, Canada. |
Dr Elizabete S. Cândido graduated in biological Sciences from Universidade Católica de Brasília (Brazil), obtained her Masters and PhD in genomic sciences and biotechnology, Universidade de Brasília (Brazil). As part of her doctoral training, she conducted research at the Institute for Molecular Bioscience, The University of Queensland (Australia). She is currently a visiting professor at Universidade Católica Dom Bosco (Brazil). With over 15 years of experience in plant peptide prospection and applied microbiology, her research focuses on antimicrobial peptides and biocosmetics. She has authored >30 publications in leading international journals. |
Ludovico Migliolo holds a degree in Biological Sciences and a Master’s in biochemistry from UFRN, and a Ph.D. in genomic sciences and biotechnology from UCB, including a sandwich PhD at The University of Queensland under Prof. David J. Craik. His research focuses on bioactive peptides for controlling pathogenic microorganisms, integrating computational, biochemical and biophysical approaches. Currently a professor at the Universidade Católica Dom Bosco (UCDB), he works on protein purification, sequencing, molecular modelling, and peptide design. His collaborations with Prof. Craik yielded notable publications, and his studies explore antimicrobial, immunomodulatory, and toxin-inspired peptides for health and agribusiness applications. |
Prof. Marlon H. Cardoso graduated in biological sciences from Universidade Católica de Brasília (Brazil) and obtained his PhD in molecular pathology from the Faculty of Medicine, Universidade de Brasília (Brazil). As part of his doctoral training, he conducted research at the Institute for Molecular Bioscience, The University of Queensland (Australia). He is currently a principal investigator, assistant professor and lecturer at Universidade Católica Dom Bosco (Brazil). With over 12 years of experience in peptide drug design, his research focuses on antimicrobial peptides and peptidomimetics, integrating computational and experimental strategies to explore their structure, function and mechanisms of action. He has received multiple awards and authored >90 publications in leading international journals. |
Octávio Luiz Franco is a professor and coordinator of the Biotechnology Program at Universidade Católica Dom Bosco. He holds a PhD in biological sciences from the University of Brasília and completed postdoctoral training at Embrapa and the University of Edinburgh. A CNPq Level 1A Researcher, he has published over 550 scientific papers in leading journals and holds nearly 40 patents, including the anti-aging product OS-1. He co-founded Peptidus, Lumis, and SO Biotech, focusing on biotechnology and health. He has supervised over 120 graduate students and is actively involved in science communication through lectures, media and social media platforms. |
Abstract
Antimicrobial resistance (AMR) is a global health problem, therefore, anti-AMR alternatives and strategies are required to develop effective therapeutics. Bearing this in mind, macrocyclic peptides (MCPs) that present cyclic scaffolds, disulfide bonds and constrained arrangements offer a distinct structural advantage that expands their potential mechanisms of action against pathogens. By modifying and improving this class of peptides, it is possible to obtain greater stability under extreme biological conditions and extended therapeutic windows, also enabling targeted action against intracellular pathogens. These advancements are driven by integrating computational tools, including artificial intelligence, to predict optimal sequences based on amino acid motifs, patterns, and physicochemical properties. Altogether, these approaches help us to design optimised MCPs and facilitate the development of more robust, selective and effective therapeutic agents tailored to combat AMR. In this review, we will explore recent advances in the context of AMR, integrating computational approaches for MCPs design, and proposed mechanisms of action for the next generation of MCP-based therapeutics.
Keywords: antimicrobial peptides, antimicrobial resistance, cell penetrating peptides, computational tools, macrocyclic peptides, next-generation therapeutics, peptide grafting, peptide internalisation.
Dr Samilla Beatriz de Rezende received her PhD in biotechnology from Universidade Católica Dom Bosco. She was a visiting PhD student at the Institute for Molecular Bioscience, The University of Queensland, Australia, in Prof. David Craik’s lab, and worked with Prof. Marlon H. Cardoso’s group and Prof. Octávio Franco’s lab on antimicrobial peptides and peptidomimetics. Her research focuses on rational peptide design, bioinformatics, and structural biophysics. Moreover, she has authored 12 international journal articles, contributed to book chapters and scientific conferences, and is co-inventor of a patent. She is currently a Postdoctoral Research Fellow in the MICRO Lab at the University of Alberta, Canada. |
Dr Elizabete S. Cândido graduated in biological Sciences from Universidade Católica de Brasília (Brazil), obtained her Masters and PhD in genomic sciences and biotechnology, Universidade de Brasília (Brazil). As part of her doctoral training, she conducted research at the Institute for Molecular Bioscience, The University of Queensland (Australia). She is currently a visiting professor at Universidade Católica Dom Bosco (Brazil). With over 15 years of experience in plant peptide prospection and applied microbiology, her research focuses on antimicrobial peptides and biocosmetics. She has authored >30 publications in leading international journals. |
Ludovico Migliolo holds a degree in Biological Sciences and a Master’s in biochemistry from UFRN, and a Ph.D. in genomic sciences and biotechnology from UCB, including a sandwich PhD at The University of Queensland under Prof. David J. Craik. His research focuses on bioactive peptides for controlling pathogenic microorganisms, integrating computational, biochemical and biophysical approaches. Currently a professor at the Universidade Católica Dom Bosco (UCDB), he works on protein purification, sequencing, molecular modelling, and peptide design. His collaborations with Prof. Craik yielded notable publications, and his studies explore antimicrobial, immunomodulatory, and toxin-inspired peptides for health and agribusiness applications. |
Prof. Marlon H. Cardoso graduated in biological sciences from Universidade Católica de Brasília (Brazil) and obtained his PhD in molecular pathology from the Faculty of Medicine, Universidade de Brasília (Brazil). As part of his doctoral training, he conducted research at the Institute for Molecular Bioscience, The University of Queensland (Australia). He is currently a principal investigator, assistant professor and lecturer at Universidade Católica Dom Bosco (Brazil). With over 12 years of experience in peptide drug design, his research focuses on antimicrobial peptides and peptidomimetics, integrating computational and experimental strategies to explore their structure, function and mechanisms of action. He has received multiple awards and authored >90 publications in leading international journals. |
Octávio Luiz Franco is a professor and coordinator of the Biotechnology Program at Universidade Católica Dom Bosco. He holds a PhD in biological sciences from the University of Brasília and completed postdoctoral training at Embrapa and the University of Edinburgh. A CNPq Level 1A Researcher, he has published over 550 scientific papers in leading journals and holds nearly 40 patents, including the anti-aging product OS-1. He co-founded Peptidus, Lumis, and SO Biotech, focusing on biotechnology and health. He has supervised over 120 graduate students and is actively involved in science communication through lectures, media and social media platforms. |
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