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

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 effic...

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Published inNature 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
LanguageEnglish
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
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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. 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.
AbstractList 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.
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 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.
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.
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 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 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.
ArticleNumber 1464
Author Wang, Tiannyu
Haney, Evan F.
Clancy, Gerard J.
Hamdan, Samir M.
Hong, Pei-Ying
Pantoja-Angles, Aarón
Ayach, Maya
Hancock, Robert E. W.
Ali, Zahir
Tehseen, Muhammad
Hauser, Charlotte
Mahfouz, Magdy
Alshehri, Salwa
Chaudhary, Shahid
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/36928189$$D View this record in MEDLINE/PubMed
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Snippet Antimicrobial peptides (AMPs) are promising next-generation antibiotics that can be used to combat drug-resistant pathogens. However, the high cost involved in...
Antimicrobial peptides (AMPs) are next-generation antibiotics that can be used to combat drugresistant pathogens. Here, the authors report efficient production...
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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
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Humanities and Social Sciences
Industrial applications
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multidisciplinary
Nicotiana - chemistry
Nicotiana - genetics
Nicotiana benthamiana
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Pathogens
Peptides
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Science
Science (multidisciplinary)
Synergism
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Title Efficient in planta production of amidated antimicrobial peptides that are active against drug-resistant ESKAPE pathogens
URI https://link.springer.com/article/10.1038/s41467-023-37003-z
https://www.ncbi.nlm.nih.gov/pubmed/36928189
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https://pubmed.ncbi.nlm.nih.gov/PMC10020429
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