@article{a9d487e565cc46b9b44520170728a333,
title = "Efficient in planta production of amidated antimicrobial peptides that are active against drug-resistant ESKAPE pathogens",
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.",
author = "Shahid Chaudhary and Zahir Ali and Muhammad Tehseen and Haney, {Evan F.} and Aar{\'o}n Pantoja-Angles and Salwa Alshehri and Tiannyu Wang and Clancy, {Gerard J.} and Maya Ayach and Charlotte Hauser and Hong, {Pei Ying} and Hamdan, {Samir M.} and Hancock, {Robert E.W.} and Magdy Mahfouz",
note = "Funding Information: This work was supported by BAS/1/1035-01-01 baseline and KAUST Smart Health Initiative (KSHI) funding to MM with additional support to REWH from the Canadian Institutes for Health Research FDN-154287 to REWH. We would like to thank Prof. Betty Eipper at University of Connecticut Health Center, USA for the generous gift of plasmid DNA encoding rat variants of PAM enzymes. We would like to thank Dr. Roger Plaut from Center of Biologics and Research, US Food and Drug Administration, for the generous gift of luminescent version of clinical S. aureus USA300 strain NRS384. We would like to thank Prof. Frank Sainsbury and Prof. George Lomonossoff for the generous gift of pEAQ-HT vector. We would like to thank Prof. Dirk G{\"o}rlich for the generous gift of plasmid expressing SENP protease (pAV0679, Addgene plasmid #149689). We would also like to thank Miriam Amah, Senior Technical Specialist of KAUST, for helping with ESI-MS optimization. EuH Funding Information: This work was supported by BAS/1/1035-01-01 baseline and KAUST Smart Health Initiative (KSHI) funding to MM with additional support to REWH from the Canadian Institutes for Health Research FDN-154287 to REWH. We would like to thank Prof. Betty Eipper at University of Connecticut Health Center, USA for the generous gift of plasmid DNA encoding rat variants of PAM enzymes. We would like to thank Dr. Roger Plaut from Center of Biologics and Research, US Food and Drug Administration, for the generous gift of luminescent version of clinical S. aureus USA300 strain NRS384. We would like to thank Prof. Frank Sainsbury and Prof. George Lomonossoff for the generous gift of pEAQ-HT vector. We would like to thank Prof. Dirk G{\"o}rlich for the generous gift of plasmid expressing SENPEuHprotease (pAV0679, Addgene plasmid #149689). We would also like to thank Miriam Amah, Senior Technical Specialist of KAUST, for helping with ESI-MS optimization. Publisher Copyright: {\textcopyright} 2023, The Author(s).",
year = "2023",
month = dec,
doi = "10.1038/s41467-023-37003-z",
language = "English (US)",
volume = "14",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Research",
number = "1",
}