Inhibition of translation termination by the antimicrobial peptide Drosocin

Mangano, Kyle; Klepacki, Dorota; Ohanmu, Irueosa; Baliga, Chetana; Huang, Weiping; Brakel, Alexandra; Krizsan, Andor; Polikanov, Yury S.; Hoffmann, Ralf; Vázquez‐Laslop, Nora; Mankin, Alexander S.

doi:10.1038/s41589-023-01300-x

Cited by 14 publications

(9 citation statements)

References 53 publications

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“…The ability of the synthetic peptides to induce stop codon readthrough activity was tested using the pRXG reporter plasmid that carries the rfp and gfp genes encoding red and green fluorescent proteins, respectively . In the pRXG(UGA) plasmid, the in-frame fused rfp and gfp genes are separated by a UGA stop codon . Placing a drop of the PrAMP on the surface of the agar plate inoculated with E.…”

Section: Resultsmentioning

confidence: 99%

Structure–Activity Relationships of the Antimicrobial Peptide Natural Product Apidaecin

Skowron,

Baliga,

Johnson

et al. 2023

J. Med. Chem.

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With the growing crisis of antimicrobial resistance, it is critical to continue to seek out new sources of novel antibiotics. This need has led to renewed interest in natural product antimicrobials, specifically antimicrobial peptides. Nonlytic antimicrobial peptides are highly promising due to their unique mechanisms of action. One such peptide is apidaecin (Api), which inhibits translation termination through stabilization of the quaternary complex of the ribosome-apidaecin-tRNA-release factor. Synthetic derivatives of apidaecin have been developed, but structure-guided modifications have yet to be considered. In this work, we have focused on modifying key residues in the Api sequence that are responsible for the interactions that stabilize the quaternary complex. We present one of the first examples of a highly modified Api peptide that maintains its antimicrobial activity and interaction with the translation complex. These findings establish a starting point for further structure-guided optimization of Api peptides.

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Section: Resultsmentioning

confidence: 99%

Structure–Activity Relationships of the Antimicrobial Peptide Natural Product Apidaecin

Skowron,

Baliga,

Johnson

et al. 2023

J. Med. Chem.

Self Cite

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“…This suggests their specificity is instead owing to differences in their binding affinity for the microbes they target. Drosocin has many functional analogues across insect immune systems [ 18 , 55 , 56 ]. The specific importance of Drosocin against Enterobacter cloacae [ 23 , 47 ], coupled with recent data showing that Drosocin binds to bacterial ribosomes to inhibit translation [ 55 , 57 ], suggests a characteristic of the Enterobacter cloacae ribosome could make it specifically susceptible to Drosocin attack.…”

Section: The ‘Achilles Principle’ Of Immune Evolutionmentioning

confidence: 99%

“…Drosocin has many functional analogues across insect immune systems [ 18 , 55 , 56 ]. The specific importance of Drosocin against Enterobacter cloacae [ 23 , 47 ], coupled with recent data showing that Drosocin binds to bacterial ribosomes to inhibit translation [ 55 , 57 ], suggests a characteristic of the Enterobacter cloacae ribosome could make it specifically susceptible to Drosocin attack. Other mediators of Drosocin-bacteria specificity could include cell membrane components such as uptake permeases, which import Drosocin-like peptides into the cell [ 56 , 58 ], a prerequisite for ensuing ribosome attack.…”

Section: The ‘Achilles Principle’ Of Immune Evolutionmentioning

confidence: 99%

When the microbiome shapes the host: immune evolution implications for infectious disease

Hanson

2024

Phil. Trans. R. Soc. B

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The microbiome includes both ‘mutualist’ and ‘pathogen’ microbes, regulated by the same innate immune architecture. A major question has therefore been: how do hosts prevent pathogenic infections while maintaining beneficial microbes? One idea suggests hosts can selectively activate innate immunity upon pathogenic infection, but not mutualist colonization. Another idea posits that hosts can selectively attack pathogens, but not mutualists. Here I review evolutionary principles of microbe recognition and immune activation, and reflect on newly observed immune effector–microbe specificity perhaps supporting the latter idea. Recent work in Drosophila has found a surprising importance for single antimicrobial peptides in combatting specific ecologically relevant microbes. The developing picture suggests these effectors have evolved for this purpose. Other defence responses like reactive oxygen species bursts can also be uniquely effective against specific microbes. Signals in other model systems including nematodes, Hydra , oysters, and mammals, suggest that effector–microbe specificity may be a fundamental principle of host–pathogen interactions. I propose this effector–microbe specificity stems from weaknesses of the microbes themselves: if microbes have intrinsic weaknesses, hosts can evolve effectors that exploit those weaknesses. I define this host–microbe relationship as ‘the Achilles principle of immune evolution’. Incorporating this view helps interpret why some host–microbe interactions develop in a coevolutionary framework (e.g. Red Queen dynamics), or as a one-sided evolutionary response. This clarification should be valuable to better understand the principles behind host susceptibilities to infectious diseases. This article is part of the theme issue ‘Sculpting the microbiome: how host factors determine and respond to microbial colonization’.

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“…They then extracted peptides from fly samples and later purified them using chromatography and mass spectrometry. The purified peptides were then subjected to further characterization to determine their chemical structure, activity, and mode of action [76,77]. A similar approach was followed for melittin as well [78].…”

Section: Discovery Of Ampsmentioning

confidence: 99%

Shaping the Future of Antimicrobial Therapy: Harnessing the Power of Antimicrobial Peptides in Biomedical Applications

Tripathi,

Singh,

Trivedi

et al. 2023

JFB

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Antimicrobial peptides (AMPs) have emerged as a promising class of bioactive molecules with the potential to combat infections associated with medical implants and biomaterials. This review article aims to provide a comprehensive analysis of the role of antimicrobial peptides in medical implants and biomaterials, along with their diverse clinical applications. The incorporation of AMPs into various medical implants and biomaterials has shown immense potential in mitigating biofilm formation and preventing implant-related infections. We review the latest advancements in biomedical sciences and discuss the AMPs that were immobilized successfully to enhance their efficacy and stability within the implant environment. We also highlight successful examples of AMP coatings for the treatment of surgical site infections (SSIs), contact lenses, dental applications, AMP-incorporated bone grafts, urinary tract infections (UTIs), medical implants, etc. Additionally, we discuss the potential challenges and prospects of AMPs in medical implants, such as effectiveness, instability and implant-related complications. We also discuss strategies that can be employed to overcome the limitations of AMP-coated biomaterials for prolonged longevity in clinical settings.

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Inhibition of translation termination by the antimicrobial peptide Drosocin

Cited by 14 publications

References 53 publications

Structure–Activity Relationships of the Antimicrobial Peptide Natural Product Apidaecin

Structure–Activity Relationships of the Antimicrobial Peptide Natural Product Apidaecin

When the microbiome shapes the host: immune evolution implications for infectious disease

Shaping the Future of Antimicrobial Therapy: Harnessing the Power of Antimicrobial Peptides in Biomedical Applications

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