Whole microbe arrays accurately predict interactions and overall antimicrobial activity of galectin-8 toward distinct strains of Streptococcus pneumoniae

Abstract Microbial glycan microarrays (MGMs) populated with purified microbial glycans have been used to define the specificity of host immune factors toward microbes in a high throughput manner. However, a limitation of such arrays is that glycan presentation may not fully recapitulate the natural...

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Main Authors: Shang-Chuen Wu, Hau-Ming Jan, Mary L. Vallecillo-Zúniga, Matthew F. Rathgeber, Caleb S. Stowell, Kaleb L. Murdock, Kashyap R. Patel, Hirotomo Nakahara, Carter J. Stowell, Moon H. Nahm, Connie M. Arthur, Richard D. Cummings, Sean R. Stowell
Format: Article
Language:English
Published: Nature Portfolio 2023-04-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-023-27964-y
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author Shang-Chuen Wu
Hau-Ming Jan
Mary L. Vallecillo-Zúniga
Matthew F. Rathgeber
Caleb S. Stowell
Kaleb L. Murdock
Kashyap R. Patel
Hirotomo Nakahara
Carter J. Stowell
Moon H. Nahm
Connie M. Arthur
Richard D. Cummings
Sean R. Stowell
author_facet Shang-Chuen Wu
Hau-Ming Jan
Mary L. Vallecillo-Zúniga
Matthew F. Rathgeber
Caleb S. Stowell
Kaleb L. Murdock
Kashyap R. Patel
Hirotomo Nakahara
Carter J. Stowell
Moon H. Nahm
Connie M. Arthur
Richard D. Cummings
Sean R. Stowell
author_sort Shang-Chuen Wu
collection DOAJ
description Abstract Microbial glycan microarrays (MGMs) populated with purified microbial glycans have been used to define the specificity of host immune factors toward microbes in a high throughput manner. However, a limitation of such arrays is that glycan presentation may not fully recapitulate the natural presentation that exists on microbes. This raises the possibility that interactions observed on the array, while often helpful in predicting actual interactions with intact microbes, may not always accurately ascertain the overall affinity of a host immune factor for a given microbe. Using galectin-8 (Gal-8) as a probe, we compared the specificity and overall affinity observed using a MGM populated with glycans harvested from various strains of Streptococcus pneumoniae to an intact microbe microarray (MMA). Our results demonstrate that while similarities in binding specificity between the MGM and MMA are apparent, Gal-8 binding toward the MMA more accurately predicted interactions with strains of S. pneumoniae, including the overall specificity of Gal-8 antimicrobial activity. Taken together, these results not only demonstrate that Gal-8 possesses antimicrobial activity against distinct strains of S. pneumoniae that utilize molecular mimicry, but that microarray platforms populated with intact microbes present an advantageous strategy when exploring host interactions with microbes.
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spelling doaj.art-c4280ad7b7c745f8a5a8f62ba788f3bd2023-04-03T05:23:32ZengNature PortfolioScientific Reports2045-23222023-04-0113111410.1038/s41598-023-27964-yWhole microbe arrays accurately predict interactions and overall antimicrobial activity of galectin-8 toward distinct strains of Streptococcus pneumoniaeShang-Chuen Wu0Hau-Ming Jan1Mary L. Vallecillo-Zúniga2Matthew F. Rathgeber3Caleb S. Stowell4Kaleb L. Murdock5Kashyap R. Patel6Hirotomo Nakahara7Carter J. Stowell8Moon H. Nahm9Connie M. Arthur10Richard D. Cummings11Sean R. Stowell12Joint Program in Transfusion Medicine, Department of Pathology, Brigham and Women’s Hospital, National Center for Functional Glycomics, 630E New Research Building, Harvard Medical SchoolJoint Program in Transfusion Medicine, Department of Pathology, Brigham and Women’s Hospital, National Center for Functional Glycomics, 630E New Research Building, Harvard Medical SchoolJoint Program in Transfusion Medicine, Department of Pathology, Brigham and Women’s Hospital, National Center for Functional Glycomics, 630E New Research Building, Harvard Medical SchoolJoint Program in Transfusion Medicine, Department of Pathology, Brigham and Women’s Hospital, National Center for Functional Glycomics, 630E New Research Building, Harvard Medical SchoolJoint Program in Transfusion Medicine, Department of Pathology, Brigham and Women’s Hospital, National Center for Functional Glycomics, 630E New Research Building, Harvard Medical SchoolJoint Program in Transfusion Medicine, Department of Pathology, Brigham and Women’s Hospital, National Center for Functional Glycomics, 630E New Research Building, Harvard Medical SchoolJoint Program in Transfusion Medicine, Department of Pathology, Brigham and Women’s Hospital, National Center for Functional Glycomics, 630E New Research Building, Harvard Medical SchoolJoint Program in Transfusion Medicine, Department of Pathology, Brigham and Women’s Hospital, National Center for Functional Glycomics, 630E New Research Building, Harvard Medical SchoolJoint Program in Transfusion Medicine, Department of Pathology, Brigham and Women’s Hospital, National Center for Functional Glycomics, 630E New Research Building, Harvard Medical SchoolDepartment of Medicine, University of Alabama at BirminghamJoint Program in Transfusion Medicine, Department of Pathology, Brigham and Women’s Hospital, National Center for Functional Glycomics, 630E New Research Building, Harvard Medical SchoolHarvard Glycomics Center, Beth Israel Deaconess Medical Center, Harvard Medical SchoolJoint Program in Transfusion Medicine, Department of Pathology, Brigham and Women’s Hospital, National Center for Functional Glycomics, 630E New Research Building, Harvard Medical SchoolAbstract Microbial glycan microarrays (MGMs) populated with purified microbial glycans have been used to define the specificity of host immune factors toward microbes in a high throughput manner. However, a limitation of such arrays is that glycan presentation may not fully recapitulate the natural presentation that exists on microbes. This raises the possibility that interactions observed on the array, while often helpful in predicting actual interactions with intact microbes, may not always accurately ascertain the overall affinity of a host immune factor for a given microbe. Using galectin-8 (Gal-8) as a probe, we compared the specificity and overall affinity observed using a MGM populated with glycans harvested from various strains of Streptococcus pneumoniae to an intact microbe microarray (MMA). Our results demonstrate that while similarities in binding specificity between the MGM and MMA are apparent, Gal-8 binding toward the MMA more accurately predicted interactions with strains of S. pneumoniae, including the overall specificity of Gal-8 antimicrobial activity. Taken together, these results not only demonstrate that Gal-8 possesses antimicrobial activity against distinct strains of S. pneumoniae that utilize molecular mimicry, but that microarray platforms populated with intact microbes present an advantageous strategy when exploring host interactions with microbes.https://doi.org/10.1038/s41598-023-27964-y
spellingShingle Shang-Chuen Wu
Hau-Ming Jan
Mary L. Vallecillo-Zúniga
Matthew F. Rathgeber
Caleb S. Stowell
Kaleb L. Murdock
Kashyap R. Patel
Hirotomo Nakahara
Carter J. Stowell
Moon H. Nahm
Connie M. Arthur
Richard D. Cummings
Sean R. Stowell
Whole microbe arrays accurately predict interactions and overall antimicrobial activity of galectin-8 toward distinct strains of Streptococcus pneumoniae
Scientific Reports
title Whole microbe arrays accurately predict interactions and overall antimicrobial activity of galectin-8 toward distinct strains of Streptococcus pneumoniae
title_full Whole microbe arrays accurately predict interactions and overall antimicrobial activity of galectin-8 toward distinct strains of Streptococcus pneumoniae
title_fullStr Whole microbe arrays accurately predict interactions and overall antimicrobial activity of galectin-8 toward distinct strains of Streptococcus pneumoniae
title_full_unstemmed Whole microbe arrays accurately predict interactions and overall antimicrobial activity of galectin-8 toward distinct strains of Streptococcus pneumoniae
title_short Whole microbe arrays accurately predict interactions and overall antimicrobial activity of galectin-8 toward distinct strains of Streptococcus pneumoniae
title_sort whole microbe arrays accurately predict interactions and overall antimicrobial activity of galectin 8 toward distinct strains of streptococcus pneumoniae
url https://doi.org/10.1038/s41598-023-27964-y
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