Monoclonal IgM Antibodies Targeting Candida albicans Hyr1 Provide Cross-Kingdom Protection Against Gram-Negative Bacteria
Recent years have seen an unprecedented rise in the incidence of multidrug-resistant (MDR) Gram-negative bacteria (GNBs) such as Acinetobacter and Klebsiella species. In view of the shortage of novel drugs in the pipeline, alternative strategies to prevent, and treat infections by GNBs are urgently...
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Format: | Article |
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Frontiers Media S.A.
2020-02-01
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Series: | Frontiers in Immunology |
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Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2020.00076/full |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Eman G. Youssef Eman G. Youssef Eman G. Youssef Lina Zhang Lina Zhang Sondus Alkhazraji Sondus Alkhazraji Teclegiorgis Gebremariam Teclegiorgis Gebremariam Shakti Singh Shakti Singh Nannette Y. Yount Nannette Y. Yount Michael R. Yeaman Michael R. Yeaman Michael R. Yeaman Michael R. Yeaman Priya Uppuluri Priya Uppuluri Priya Uppuluri Ashraf S. Ibrahim Ashraf S. Ibrahim Ashraf S. Ibrahim |
spellingShingle |
Eman G. Youssef Eman G. Youssef Eman G. Youssef Lina Zhang Lina Zhang Sondus Alkhazraji Sondus Alkhazraji Teclegiorgis Gebremariam Teclegiorgis Gebremariam Shakti Singh Shakti Singh Nannette Y. Yount Nannette Y. Yount Michael R. Yeaman Michael R. Yeaman Michael R. Yeaman Michael R. Yeaman Priya Uppuluri Priya Uppuluri Priya Uppuluri Ashraf S. Ibrahim Ashraf S. Ibrahim Ashraf S. Ibrahim Monoclonal IgM Antibodies Targeting Candida albicans Hyr1 Provide Cross-Kingdom Protection Against Gram-Negative Bacteria Frontiers in Immunology monoclonal antibodies Candida Hyr1 Acinetobacter baumannii Klebsiella pneumoniae passive vaccine molecular modeling |
author_facet |
Eman G. Youssef Eman G. Youssef Eman G. Youssef Lina Zhang Lina Zhang Sondus Alkhazraji Sondus Alkhazraji Teclegiorgis Gebremariam Teclegiorgis Gebremariam Shakti Singh Shakti Singh Nannette Y. Yount Nannette Y. Yount Michael R. Yeaman Michael R. Yeaman Michael R. Yeaman Michael R. Yeaman Priya Uppuluri Priya Uppuluri Priya Uppuluri Ashraf S. Ibrahim Ashraf S. Ibrahim Ashraf S. Ibrahim |
author_sort |
Eman G. Youssef |
title |
Monoclonal IgM Antibodies Targeting Candida albicans Hyr1 Provide Cross-Kingdom Protection Against Gram-Negative Bacteria |
title_short |
Monoclonal IgM Antibodies Targeting Candida albicans Hyr1 Provide Cross-Kingdom Protection Against Gram-Negative Bacteria |
title_full |
Monoclonal IgM Antibodies Targeting Candida albicans Hyr1 Provide Cross-Kingdom Protection Against Gram-Negative Bacteria |
title_fullStr |
Monoclonal IgM Antibodies Targeting Candida albicans Hyr1 Provide Cross-Kingdom Protection Against Gram-Negative Bacteria |
title_full_unstemmed |
Monoclonal IgM Antibodies Targeting Candida albicans Hyr1 Provide Cross-Kingdom Protection Against Gram-Negative Bacteria |
title_sort |
monoclonal igm antibodies targeting candida albicans hyr1 provide cross-kingdom protection against gram-negative bacteria |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2020-02-01 |
description |
Recent years have seen an unprecedented rise in the incidence of multidrug-resistant (MDR) Gram-negative bacteria (GNBs) such as Acinetobacter and Klebsiella species. In view of the shortage of novel drugs in the pipeline, alternative strategies to prevent, and treat infections by GNBs are urgently needed. Previously, we have reported that the Candida albicans hypha-regulated protein Hyr1 shares striking three-dimensional structural homology with cell surface proteins of Acinetobacter baumannii. Moreover, active vaccination with rHyr1p-N or passive immunization with anti-Hyr1p polyclonal antibody protects mice from Acinetobacter infection. In the present study, we use molecular modeling to guide design of monoclonal antibodies (mAbs) generated against Hyr1p and show them to bind to priority surface antigens of Acinetobacter and Klebsiella pneumoniae. The anti-Hyr1 mAbs block damage to primary endothelial cells induced by the bacteria and protect mice from lethal pulmonary infections mediated by A. baumannii or K. pneumoniae. Our current studies emphasize the potential of harnessing Hyr1p mAbs as a cross-kingdom immunotherapeutic strategy against MDR GNBs. |
topic |
monoclonal antibodies Candida Hyr1 Acinetobacter baumannii Klebsiella pneumoniae passive vaccine molecular modeling |
url |
https://www.frontiersin.org/article/10.3389/fimmu.2020.00076/full |
work_keys_str_mv |
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doaj-4641354e927447fcafb61d17fbeba1e62020-11-25T01:45:02ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-02-011110.3389/fimmu.2020.00076503573Monoclonal IgM Antibodies Targeting Candida albicans Hyr1 Provide Cross-Kingdom Protection Against Gram-Negative BacteriaEman G. Youssef0Eman G. Youssef1Eman G. Youssef2Lina Zhang3Lina Zhang4Sondus Alkhazraji5Sondus Alkhazraji6Teclegiorgis Gebremariam7Teclegiorgis Gebremariam8Shakti Singh9Shakti Singh10Nannette Y. Yount11Nannette Y. Yount12Michael R. Yeaman13Michael R. Yeaman14Michael R. Yeaman15Michael R. Yeaman16Priya Uppuluri17Priya Uppuluri18Priya Uppuluri19Ashraf S. Ibrahim20Ashraf S. Ibrahim21Ashraf S. Ibrahim22Division of Infectious Diseases, Harbor-UCLA Medical Center, Torrance, CA, United StatesThe Lundquist Institute for Biomedical Innovation, Harbor-UCLA Medical Center, Torrance, CA, United StatesDepartment of Biotechnology and Life Sciences, Faculty of Postgraduate Studies for Advanced Sciences, Beni-Suef University, Beni-Suef, EgyptDivision of Infectious Diseases, Harbor-UCLA Medical Center, Torrance, CA, United StatesCollege of Wildlife Resources, Northeast Forestry University, Harbin, ChinaDivision of Infectious Diseases, Harbor-UCLA Medical Center, Torrance, CA, United StatesThe Lundquist Institute for Biomedical Innovation, Harbor-UCLA Medical Center, Torrance, CA, United StatesDivision of Infectious Diseases, Harbor-UCLA Medical Center, Torrance, CA, United StatesThe Lundquist Institute for Biomedical Innovation, Harbor-UCLA Medical Center, Torrance, CA, United StatesDivision of Infectious Diseases, Harbor-UCLA Medical Center, Torrance, CA, United StatesThe Lundquist Institute for Biomedical Innovation, Harbor-UCLA Medical Center, Torrance, CA, United StatesDivision of Infectious Diseases, Harbor-UCLA Medical Center, Torrance, CA, United StatesDivision of Molecular Medicine, Harbor-UCLA Medical Center, Torrance, CA, United StatesDivision of Infectious Diseases, Harbor-UCLA Medical Center, Torrance, CA, United StatesThe Lundquist Institute for Biomedical Innovation, Harbor-UCLA Medical Center, Torrance, CA, United StatesDivision of Molecular Medicine, Harbor-UCLA Medical Center, Torrance, CA, United StatesDepartment of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, United StatesDivision of Infectious Diseases, Harbor-UCLA Medical Center, Torrance, CA, United StatesThe Lundquist Institute for Biomedical Innovation, Harbor-UCLA Medical Center, Torrance, CA, United StatesDepartment of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, United StatesDivision of Infectious Diseases, Harbor-UCLA Medical Center, Torrance, CA, United StatesThe Lundquist Institute for Biomedical Innovation, Harbor-UCLA Medical Center, Torrance, CA, United StatesDepartment of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, United StatesRecent years have seen an unprecedented rise in the incidence of multidrug-resistant (MDR) Gram-negative bacteria (GNBs) such as Acinetobacter and Klebsiella species. In view of the shortage of novel drugs in the pipeline, alternative strategies to prevent, and treat infections by GNBs are urgently needed. Previously, we have reported that the Candida albicans hypha-regulated protein Hyr1 shares striking three-dimensional structural homology with cell surface proteins of Acinetobacter baumannii. Moreover, active vaccination with rHyr1p-N or passive immunization with anti-Hyr1p polyclonal antibody protects mice from Acinetobacter infection. In the present study, we use molecular modeling to guide design of monoclonal antibodies (mAbs) generated against Hyr1p and show them to bind to priority surface antigens of Acinetobacter and Klebsiella pneumoniae. The anti-Hyr1 mAbs block damage to primary endothelial cells induced by the bacteria and protect mice from lethal pulmonary infections mediated by A. baumannii or K. pneumoniae. Our current studies emphasize the potential of harnessing Hyr1p mAbs as a cross-kingdom immunotherapeutic strategy against MDR GNBs.https://www.frontiersin.org/article/10.3389/fimmu.2020.00076/fullmonoclonal antibodiesCandida Hyr1Acinetobacter baumanniiKlebsiella pneumoniaepassive vaccinemolecular modeling |