Efficient in planta production of amidated antimicrobial peptides that are active against drug-resistant ESKAPE pathogens

• Published in: Nature communications Vol. 14; no. 1; pp. 1464 - 16
• Main Authors: Chaudhary, Shahid, Ali, Zahir, Tehseen, Muhammad, Haney, Evan F., Pantoja-Angles, Aarón, Alshehri, Salwa, Wang, Tiannyu, Clancy, Gerard J., Ayach, Maya, Hauser, Charlotte, Hong, Pei-Ying, Hamdan, Samir M., Hancock, Robert E. W., Mahfouz, Magdy
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 16.03.2023; Nature Publishing Group; Nature Portfolio
• Subjects: 38/109; 38/44; 42; 631/1647/1511; 631/449/447/2311; 631/61/447/2311; 631/61/51/2313; 82/16; 82/29; 82/58; 82/80; 82/81; 82/83; Animals; Anti-Bacterial Agents - biosynthesis; Anti-Bacterial Agents - pharmacology; Antibiotic resistance; Antibiotics; Antiinfectives and antibacterials; Antimicrobial agents; Antimicrobial Cationic Peptides - biosynthesis; Antimicrobial Cationic Peptides - pharmacology; Antimicrobial peptides; Antimicrobial Peptides - biosynthesis; Biofilms; Biological activity; Drug resistance; Drug Resistance, Bacterial - drug effects; Economic analysis; Economics; Enzymes; Glycine; Humanities and Social Sciences; Industrial applications; Mammals; multidisciplinary; Nicotiana - chemistry; Nicotiana - genetics; Nicotiana benthamiana; Oxygenase; Pathogens; Peptides; Plants; Science; Science (multidisciplinary); Synergism; Transgenic plants
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-023-37003-z

Antimicrobial peptides (AMPs) are promising next-generation antibiotics that can be used to combat drug-resistant pathogens. However, the high cost involved in AMP synthesis and their short plasma half-life render their clinical translation a challenge. To address these shortcomings, we report efficient production of bioactive amidated AMPs by transient expression of glycine-extended AMPs in Nicotiana benthamiana line expressing the mammalian enzyme peptidylglycine α-amidating mono-oxygenase (PAM). Cationic AMPs accumulate to substantial levels in PAM transgenic plants compare to nontransgenic N. benthamiana . Moreover, AMPs purified from plants exhibit robust killing activity against six highly virulent and antibiotic resistant ESKAPE pathogens, prevent their biofilm formation, analogous to their synthetic counterparts and synergize with antibiotics. We also perform a base case techno-economic analysis of our platform, demonstrating the potential economic advantages and scalability for industrial use. Taken together, our experimental data and techno-economic analysis demonstrate the potential use of plant chassis for large-scale production of clinical-grade AMPs. Antimicrobial peptides (AMPs) are next-generation antibiotics that can be used to combat drugresistant pathogens. Here, the authors report efficient production of bioactive amidated AMPs by transient expression in Nicotiana benthamiana line expressing the mammalian enzyme peptidylglycine α-amidating mono-oxygenase.