Design of 8-mer peptides that block Clostridioides difficile toxin A in intestinal cells
Abstract Infections by Clostridioides difficile, a bacterium that targets the large intestine (colon), impact a large number of people worldwide. Bacterial colonization is mediated by two exotoxins: toxins A and B. Short peptides that can be delivered to the gut and inhibit the biocatalytic activity...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2023-08-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-023-05242-x |
| _version_ | 1797557120421330944 |
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| author | Sudeep Sarma Carly M. Catella Ellyce T. San Pedro Xingqing Xiao Deniz Durmusoglu Stefano Menegatti Nathan Crook Scott T. Magness Carol K. Hall |
| author_facet | Sudeep Sarma Carly M. Catella Ellyce T. San Pedro Xingqing Xiao Deniz Durmusoglu Stefano Menegatti Nathan Crook Scott T. Magness Carol K. Hall |
| author_sort | Sudeep Sarma |
| collection | DOAJ |
| description | Abstract Infections by Clostridioides difficile, a bacterium that targets the large intestine (colon), impact a large number of people worldwide. Bacterial colonization is mediated by two exotoxins: toxins A and B. Short peptides that can be delivered to the gut and inhibit the biocatalytic activity of these toxins represent a promising therapeutic strategy to prevent and treat C. diff. infection. We describe an approach that combines a Peptide Binding Design (PepBD) algorithm, molecular-level simulations, a rapid screening assay to evaluate peptide:toxin binding, a primary human cell-based assay, and surface plasmon resonance (SPR) measurements to develop peptide inhibitors that block Toxin A in colon epithelial cells. One peptide, SA1, is found to block TcdA toxicity in primary-derived human colon (large intestinal) epithelial cells. SA1 binds TcdA with a KD of 56.1 ± 29.8 nM as measured by surface plasmon resonance (SPR). |
| first_indexed | 2024-03-10T17:12:45Z |
| format | Article |
| id | doaj.art-0b5d86e48e79440287b7b40e3dc1173d |
| institution | Directory Open Access Journal |
| issn | 2399-3642 |
| language | English |
| last_indexed | 2024-03-10T17:12:45Z |
| publishDate | 2023-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj.art-0b5d86e48e79440287b7b40e3dc1173d2023-11-20T10:35:45ZengNature PortfolioCommunications Biology2399-36422023-08-016111310.1038/s42003-023-05242-xDesign of 8-mer peptides that block Clostridioides difficile toxin A in intestinal cellsSudeep Sarma0Carly M. Catella1Ellyce T. San Pedro2Xingqing Xiao3Deniz Durmusoglu4Stefano Menegatti5Nathan Crook6Scott T. Magness7Carol K. Hall8Department of Chemical Engineering, North Carolina State UniversityDepartment of Chemical Engineering, North Carolina State UniversityDepartment of Medicine, University of North Carolina at Chapel HillDepartment of Chemical Engineering, North Carolina State UniversityDepartment of Chemical Engineering, North Carolina State UniversityDepartment of Chemical Engineering, North Carolina State UniversityDepartment of Chemical Engineering, North Carolina State UniversityDepartment of Medicine, University of North Carolina at Chapel HillDepartment of Chemical Engineering, North Carolina State UniversityAbstract Infections by Clostridioides difficile, a bacterium that targets the large intestine (colon), impact a large number of people worldwide. Bacterial colonization is mediated by two exotoxins: toxins A and B. Short peptides that can be delivered to the gut and inhibit the biocatalytic activity of these toxins represent a promising therapeutic strategy to prevent and treat C. diff. infection. We describe an approach that combines a Peptide Binding Design (PepBD) algorithm, molecular-level simulations, a rapid screening assay to evaluate peptide:toxin binding, a primary human cell-based assay, and surface plasmon resonance (SPR) measurements to develop peptide inhibitors that block Toxin A in colon epithelial cells. One peptide, SA1, is found to block TcdA toxicity in primary-derived human colon (large intestinal) epithelial cells. SA1 binds TcdA with a KD of 56.1 ± 29.8 nM as measured by surface plasmon resonance (SPR).https://doi.org/10.1038/s42003-023-05242-x |
| spellingShingle | Sudeep Sarma Carly M. Catella Ellyce T. San Pedro Xingqing Xiao Deniz Durmusoglu Stefano Menegatti Nathan Crook Scott T. Magness Carol K. Hall Design of 8-mer peptides that block Clostridioides difficile toxin A in intestinal cells Communications Biology |
| title | Design of 8-mer peptides that block Clostridioides difficile toxin A in intestinal cells |
| title_full | Design of 8-mer peptides that block Clostridioides difficile toxin A in intestinal cells |
| title_fullStr | Design of 8-mer peptides that block Clostridioides difficile toxin A in intestinal cells |
| title_full_unstemmed | Design of 8-mer peptides that block Clostridioides difficile toxin A in intestinal cells |
| title_short | Design of 8-mer peptides that block Clostridioides difficile toxin A in intestinal cells |
| title_sort | design of 8 mer peptides that block clostridioides difficile toxin a in intestinal cells |
| url | https://doi.org/10.1038/s42003-023-05242-x |
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