Abstract:
: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.
journal_name
Front Immunoljournal_title
Frontiers in immunologyauthors
Youssef EG,Zhang L,Alkhazraji S,Gebremariam T,Singh S,Yount NY,Yeaman MR,Uppuluri P,Ibrahim ASdoi
10.3389/fimmu.2020.00076subject
Has Abstractpub_date
2020-02-18 00:00:00pages
76issn
1664-3224journal_volume
11pub_type
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journal_title:Frontiers in immunology
pub_type: 杂志文章
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journal_title:Frontiers in immunology
pub_type: 杂志文章
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journal_title:Frontiers in immunology
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journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2014.00096
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journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2020.02085
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journal_title:Frontiers in immunology
pub_type: 杂志文章
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pub_type: 杂志文章
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