Targeted Killing of Staphylococcus aureus Using Specific Peptides Displayed on Yeast Vacuoles

ABSTRACT Staphylococcus aureus is a common pathogen that causes health care-related and community-associated infections. In this study, we provide a novel system that can recognize and kill S. aureus bacteria. The system is specifically based on a combination of the phage display library technique a...

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Main Authors: Jaewoong Lee, Ngoc-Tu Nguyen, Le-Minh Tran, Yang-Hoon Kim, Jiho Min
Format: Article
Language:English
Published: American Society for Microbiology 2023-06-01
Series:Microbiology Spectrum
Subjects:
Online Access:https://journals.asm.org/doi/10.1128/spectrum.00920-23
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author Jaewoong Lee
Ngoc-Tu Nguyen
Le-Minh Tran
Yang-Hoon Kim
Jiho Min
author_facet Jaewoong Lee
Ngoc-Tu Nguyen
Le-Minh Tran
Yang-Hoon Kim
Jiho Min
author_sort Jaewoong Lee
collection DOAJ
description ABSTRACT Staphylococcus aureus is a common pathogen that causes health care-related and community-associated infections. In this study, we provide a novel system that can recognize and kill S. aureus bacteria. The system is specifically based on a combination of the phage display library technique and yeast vacuoles. A phage clone displaying a peptide capable of specific binding to a whole S. aureus cell was selected from a 12-mer phage peptide library. The peptide sequence was SVPLNSWSIFPR. The selected phage’s ability to bind specifically with S. aureus was confirmed using an enzyme-linked immunosorbent assay, and the chosen peptide was then synthesized. The results showed that the synthesized peptides displayed high affinity with S. aureus but low binding ability with other strains, including Gram-negative and Gram-positive bacteria such as Salmonella sp., Shigella spp., Escherichia coli, and Corynebacterium glutamicum. In addition, yeast vacuoles were used as a drug carrier by encapsulating daptomycin, a lipopeptide antibiotic used to treat Gram-positive bacterial infections. The expression of specific peptides at the encapsulated vacuole membrane created an efficient system that can specifically recognize and kill S. aureus bacteria. IMPORTANCE The phage display method was used to select peptides with high affinity and specificity for S. aureus, and these peptides were then induced to be expressed on the surface of yeast vacuoles. These surface-modified vacuoles can act as drug carriers, with drugs such as the lipopeptide antibiotic daptomycin loaded inside. An advantage of using yeast vacuoles as a drug carrier is that they can be easily produced through yeast culture, making the approach cost-effective and suitable for large-scale production and potential implementation in clinical settings. This novel approach offers a promising way to specifically target and eliminate S. aureus that could ultimately lead to improved treatment of bacterial infections and reduced risk of antibiotic resistance.
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spelling doaj.art-934bdd1a067b4b6eb24d4192bb5d23a02023-06-15T13:18:32ZengAmerican Society for MicrobiologyMicrobiology Spectrum2165-04972023-06-0111310.1128/spectrum.00920-23Targeted Killing of Staphylococcus aureus Using Specific Peptides Displayed on Yeast VacuolesJaewoong Lee0Ngoc-Tu Nguyen1Le-Minh Tran2Yang-Hoon Kim3Jiho Min4School of Chemical Engineering, Jeonbuk National University, Deokjin-Gu Jeonju, Jeonbuk, South KoreaSchool of Chemical Engineering, Jeonbuk National University, Deokjin-Gu Jeonju, Jeonbuk, South KoreaSchool of Chemical Engineering, Jeonbuk National University, Deokjin-Gu Jeonju, Jeonbuk, South KoreaCenter for Ecology and Environmental Toxicology (CEET), Chungbuk National University, Seowon-Gu, Cheongju, South KoreaSchool of Chemical Engineering, Jeonbuk National University, Deokjin-Gu Jeonju, Jeonbuk, South KoreaABSTRACT Staphylococcus aureus is a common pathogen that causes health care-related and community-associated infections. In this study, we provide a novel system that can recognize and kill S. aureus bacteria. The system is specifically based on a combination of the phage display library technique and yeast vacuoles. A phage clone displaying a peptide capable of specific binding to a whole S. aureus cell was selected from a 12-mer phage peptide library. The peptide sequence was SVPLNSWSIFPR. The selected phage’s ability to bind specifically with S. aureus was confirmed using an enzyme-linked immunosorbent assay, and the chosen peptide was then synthesized. The results showed that the synthesized peptides displayed high affinity with S. aureus but low binding ability with other strains, including Gram-negative and Gram-positive bacteria such as Salmonella sp., Shigella spp., Escherichia coli, and Corynebacterium glutamicum. In addition, yeast vacuoles were used as a drug carrier by encapsulating daptomycin, a lipopeptide antibiotic used to treat Gram-positive bacterial infections. The expression of specific peptides at the encapsulated vacuole membrane created an efficient system that can specifically recognize and kill S. aureus bacteria. IMPORTANCE The phage display method was used to select peptides with high affinity and specificity for S. aureus, and these peptides were then induced to be expressed on the surface of yeast vacuoles. These surface-modified vacuoles can act as drug carriers, with drugs such as the lipopeptide antibiotic daptomycin loaded inside. An advantage of using yeast vacuoles as a drug carrier is that they can be easily produced through yeast culture, making the approach cost-effective and suitable for large-scale production and potential implementation in clinical settings. This novel approach offers a promising way to specifically target and eliminate S. aureus that could ultimately lead to improved treatment of bacterial infections and reduced risk of antibiotic resistance.https://journals.asm.org/doi/10.1128/spectrum.00920-23phage displaypathogen detectiondrug carrierStaphylococcus aureuspeptide conjugationyeast vacuoles
spellingShingle Jaewoong Lee
Ngoc-Tu Nguyen
Le-Minh Tran
Yang-Hoon Kim
Jiho Min
Targeted Killing of Staphylococcus aureus Using Specific Peptides Displayed on Yeast Vacuoles
Microbiology Spectrum
phage display
pathogen detection
drug carrier
Staphylococcus aureus
peptide conjugation
yeast vacuoles
title Targeted Killing of Staphylococcus aureus Using Specific Peptides Displayed on Yeast Vacuoles
title_full Targeted Killing of Staphylococcus aureus Using Specific Peptides Displayed on Yeast Vacuoles
title_fullStr Targeted Killing of Staphylococcus aureus Using Specific Peptides Displayed on Yeast Vacuoles
title_full_unstemmed Targeted Killing of Staphylococcus aureus Using Specific Peptides Displayed on Yeast Vacuoles
title_short Targeted Killing of Staphylococcus aureus Using Specific Peptides Displayed on Yeast Vacuoles
title_sort targeted killing of staphylococcus aureus using specific peptides displayed on yeast vacuoles
topic phage display
pathogen detection
drug carrier
Staphylococcus aureus
peptide conjugation
yeast vacuoles
url https://journals.asm.org/doi/10.1128/spectrum.00920-23
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