Identification and Rational Design of Novel Antimicrobial Peptides for Plant Protection

ABSTRACTThe emergence of multidrug-resistant (MDR) pathogens underscores the need for new antimicrobial agents to overcome the resistance mechanisms of these organisms. Cationic antimicrobial peptides (CAPs) provide a potential source of new antimicrobial therapeutics. We previously characterized a lytic base unit (LBU) series of engineered CAPs (eCAPs) of 12 to 48 residues demonstrating maximum antibacterial selectivity at 24 residues. Further, Trp substitution in LBU sequences increased activity against bothP. aeruginosaandS. aureusunder challenging conditions (e.g., saline, divalent cations, and serum). Based on these findings, we hypothesized that the optimal length and, therefore, the cost for maximum eCAP activity under physiologically relevant conditions could be significantly reduced using only Arg and Trp arranged to form idealized amphipathic helices. Hence, we developed a novel peptide series, composed only of Arg and Trp, in a sequence predicted and verified by circular dichroism to fold into optimized amphipathic helices. The most effective antimicrobial activity was achieved at 12 residues in length (WR12) against a panel of both Gram-negative and Gram-positive clinical isolates, including extensively drug-resistant strains, in saline and broth culture and at various pH values. The results demonstrate that the rational design of CAPs can lead to a significant reduction in the length and the number of amino acids used in peptide design to achieve optimal potency and selectivity against specific pathogens.

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Rational Design of α-Helical Antimicrobial Peptides with Enhanced Activities and Specificity/Therapeutic Index

Journal of Biological Chemistry ◽

10.1074/jbc.m413406200 ◽

2005 ◽

Vol 280 (13) ◽

pp. 12316-12329 ◽

Cited By ~ 390

Author(s):

Yuxin Chen ◽

Colin T. Mant ◽

Susan W. Farmer ◽

Robert E. W. Hancock ◽

Michael L. Vasil ◽

...

Keyword(s):

Antimicrobial Peptides ◽

Rational Design ◽

Therapeutic Index

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De Novo Design of Antimicrobial Peptides With a Special Charge Pattern and Their Application in Combating Plant Pathogens

Frontiers in Plant Science ◽

10.3389/fpls.2021.753217 ◽

2021 ◽

Vol 12 ◽

Author(s):

Eric H. -L. Chen ◽

Cheng-Wei Weng ◽

Yi-Min Li ◽

Ming-Chin Wu ◽

Chien-Chih Yang ◽

...

Keyword(s):

Antimicrobial Activity ◽

Antimicrobial Peptides ◽

Plant Pathogens ◽

De Novo ◽

Plant Protection ◽

Acyl Chain ◽

Fatty Acyl ◽

Plant Diseases ◽

Basic Residue ◽

Wide Range

Plant diseases are important issues in agriculture, and the development of effective and environment-friendly means of disease control is crucial and highly desired. Antimicrobial peptides (AMPs) are known as potential alternatives to chemical pesticides because of their potent broad-spectrum antimicrobial activity and because they have no risk, or have only a low risk, of developing chemical-resistant pathogens. In this study, we designed a series of amphipathic helical peptides with different spatial distributions of positive charges and found that the peptides that had a special sequence pattern “BBHBBHHBBH” (“B” for basic residue and “H” for hydrophobic residue) displayed excellent bactericidal and fungicidal activities in a wide range of economically important plant pathogens. The peptides with higher helical propensity had lower antimicrobial activity. When we modified the peptides with a long acyl chain at their N-terminus, their plant protection effect improved. Our application of the fatty acyl-modified peptides on the leaves of tomato and Arabidopsis plants lessened the infection caused by Pectobacterium carotovorum subsp. carotovorum and Botrytis cinerea. Our study provides important insights on the development of more potent novel AMPs for plant protection.

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Linking sequence patterns and functionality of alpha-helical antimicrobial peptides

Bioinformatics ◽

10.1093/bioinformatics/bty1048 ◽

2018 ◽

Vol 35 (16) ◽

pp. 2713-2717 ◽

Cited By ~ 2

Author(s):

Igor E Eliseev ◽

Ivan N Terterov ◽

Anna N Yudenko ◽

Olga V Shamova

Keyword(s):

Antimicrobial Peptides ◽

Rational Design ◽

Therapeutic Potential ◽

Deep Understanding ◽

Supplementary Information ◽

Helical Conformation ◽

Efficient Design ◽

Sequence Patterns ◽

Functional Features ◽

Natural Peptides

Abstract Motivation The rational design of antimicrobial peptides (AMPs) with increased therapeutic potential requires deep understanding of the determinants of their activities. Inspired by the computational linguistic approach, we hypothesized that sequence patterns may encode the functional features of AMPs. Results We found that α-helical and β-sheet peptides have non-intersecting pattern sets and therefore constructed new sequence templates using only helical patterns. Designed peptides adopted an α-helical conformation upon binding to lipids, confirming that the method captures structural and biophysical properties. In the antimicrobial assay, 5 of 7 designed peptides exhibited activity against Gram(+) and Gram(–) bacteria, with most potent candidate comparable to best natural peptides. We thus conclude that sequence patterns comprise the structural and functional features of α-helical AMPs and guide their efficient design. Supplementary information Supplementary data are available at Bioinformatics online.

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Faculty Opinions recommendation of A linguistic model for the rational design of antimicrobial peptides.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1047876.497897 ◽

2006 ◽

Author(s):

Paul Dunman

Keyword(s):

Antimicrobial Peptides ◽

Rational Design ◽

Linguistic Model

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STRUCTURAL AND FUNCTIONAL ANALYSIS OF WAMP ANTIMICROBIAL PEPTIDES FOR THE DEVELOPMENT OF NEW ENVIRONMENTALLY FRIENDLY PLANT PROTECTION AGENTS

BIOTECHNOLOGY: STATE OF THE ART AND PERSPECTIVES ◽

10.37747/2312-640x-2020-18-81-83 ◽

2020 ◽

pp. 81-83

Author(s):

E. Istomina ◽

T. Korostyleva ◽

L. Scherbakova ◽

T. Odintsova

Keyword(s):

Functional Analysis ◽

Antimicrobial Peptides ◽

Theoretical Basis ◽

Plant Protection ◽

Environmentally Friendly ◽

Structure And Function ◽

And Function ◽

The Relationship

Analysis of the relationship between the structure and function of hevein-like antimicrobial WAMP peptides will serve as a theoretical basis for the development of new biopesticides and drug prototypes based on simpler WAMP derivatives.

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Crystal Structure of a Phospholipase D from the Plant-Associated Bacteria Serratia plymuthica Strain AS9 Reveals a Unique Arrangement of Catalytic Pocket

International Journal of Molecular Sciences ◽

10.3390/ijms22063219 ◽

2021 ◽

Vol 22 (6) ◽

pp. 3219

Author(s):

Fanghua Wang ◽

Siyu Liu ◽

Xuejing Mao ◽

Ruiguo Cui ◽

Bo Yang ◽

...

Keyword(s):

Crystal Structure ◽

Rational Design ◽

Structural Information ◽

Plant Protection ◽

Serratia Plymuthica ◽

Associated Bacteria ◽

Loop Region ◽

C Terminus ◽

Loop Conformation

Phospholipases D (PLDs) play important roles in different organisms and in vitro phospholipid modifications, which attract strong interests for investigation. However, the lack of PLD structural information has seriously hampered both the understanding of their structure–function relationships and the structure-based bioengineering of this enzyme. Herein, we presented the crystal structure of a PLD from the plant-associated bacteria Serratia plymuthica strain AS9 (SpPLD) at a resolution of 1.79 Å. Two classical HxKxxxxD (HKD) motifs were found in SpPLD and have shown high structural consistence with several PLDs in the same family. While comparing the structure of SpPLD with the previous resolved PLDs from the same family, several unique conformations on the C-terminus of the HKD motif were demonstrated to participate in the arrangement of the catalytic pocket of SpPLD. In SpPLD, an extented loop conformation between β9 and α9 (aa228–246) was found. Moreover, electrostatic surface potential showed that this loop region in SpPLD was positively charged while the corresponding loops in the two Streptomyces originated PLDs (PDB ID: 1F0I, 2ZE4/2ZE9) were neutral. The shortened loop between α10 and α11 (aa272–275) made the SpPLD unable to form the gate-like structure which existed specically in the two Streptomyces originated PLDs (PDB ID: 1F0I, 2ZE4/2ZE9) and functioned to stabilize the substrates. In contrast, the shortened loop conformation at this corresponding segment was more alike to several nucleases (Nuc, Zuc, mZuc, NucT) within the same family. Moreover, the loop composition between β11 and β12 was also different from the two Streptomyces originated PLDs (PDB ID: 1F0I, 2ZE4/2ZE9), which formed the entrance of the catalytic pocket and were closely related to substrate recognition. So far, SpPLD was the only structurally characterized PLD enzyme from Serratia. The structural information derived here not only helps for the understanding of the biological function of this enzyme in plant protection, but also helps for the understanding of the rational design of the mutant, with potential application in phospholipid modification.

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