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

Shahid Chaudhary, Zahir Ali, Muhammad Tehseen, Evan F. Haney, Aarón Pantoja-Angles, Salwa Alshehri, Tiannyu Wang, Gerard J. Clancy, Maya Ayach, Charlotte Hauser, Pei-Ying Hong, Samir M. Hamdan, Robert E. W. Hancock and Magdy Mahfouz ()
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Shahid Chaudhary: 4700 King Abdullah University of Science and Technology (KAUST)
Zahir Ali: 4700 King Abdullah University of Science and Technology (KAUST)
Muhammad Tehseen: King Abdullah University of Science and Technology (KAUST)
Evan F. Haney: University of British Columbia
Aarón Pantoja-Angles: 4700 King Abdullah University of Science and Technology (KAUST)
Salwa Alshehri: King Abdullah University of Science and Technology (KAUST)
Tiannyu Wang: King Abdullah University of Science and Technology (KAUST)
Gerard J. Clancy: King Abdullah University of Science and Technology (KAUST)
Maya Ayach: King Abdullah University of Science and Technology (KAUST)
Charlotte Hauser: King Abdullah University of Science and Technology (KAUST)
Pei-Ying Hong: King Abdullah University of Science and Technology (KAUST)
Samir M. Hamdan: King Abdullah University of Science and Technology (KAUST)
Robert E. W. Hancock: University of British Columbia
Magdy Mahfouz: 4700 King Abdullah University of Science and Technology (KAUST)

Nature Communications, 2023, vol. 14, issue 1, 1-16

Abstract: Abstract 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.

Date: 2023
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DOI: 10.1038/s41467-023-37003-z

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